2. Mitochondrial Fusion Genes and Related Proteins. The first description of the process of mitochondrial fusion was given in yeast by the end of 1960 [30], but mitochondrial dynamics were later analyzed in mammalian cellular models as well [31-33]. The discovery of the first gene encoding a protein mediator of mitochondrial fusion was made in Drosophila melanogaster [34]; this protein, fuzzy onions, is a homolog of the human mitofusins. Other molecules involved in the fusion machinery have recently been described, including Mgm1 in Saccharomyces cerevisiae, which was identified as a homolog of human OPA1 [35]. Similarly, DLP1/DRP1 and other proteins required for mitochondrial fission were first studied in yeast (Dnm1p) [36] and in Caenorhabditis elegans (DRP-1) [37], with description of the mammalian homologues following soon after [38, 39].. These in vivo studies suggested that the core requirements for mitochondrial fusion are similar in yeast and mammalian cells. This early evidence has ...

Our data demonstrate that IIGP, a member of the 47 kDa GTPase family, which participates in defense against intracellular pathogens, interacts with the microtubule-binding linker protein mHk3. The association of these GTPases with intracellular membranes suggests that these molecules modulate membrane-dependent processes (Taylor et al., 1997; Zerrahn et al., 2002). The herein identified interaction between IIGP and mHk3 provides the first evidence for a participation of IIGP in intracellular trafficking which could form the molecular basis for effector mechanisms directed against intracellular pathogens.. The recently described human hook protein family comprises three members that associate differentially with compartments of the secretory and endocytic pathways. A single hook protein (dHK) is expressed in Drosophila. Localized to endosomes, dHk participates in the formation or maturation of multivesicular bodies (MVB) (Kramer and Phistry, 1996), and loss of function results in a marked ...

Mfn2 is a mitochondrial fusion protein with a lower GTPase activity than that of Mfn1 (Ishihara et al, 2004; Neuspiel et al, 2005). On the basis of the mitochondrial fusion activity of Mfn2, the alterations in mitochondrial morphology and function detected upon silencing or ablation of this gene have been attributed to reduced mitochondrial fusion (Bach et al, 2003; Chen et al, 2003; Pich et al, 2005). Here we provide evidence that an ER‐related mechanism is responsible for the development of swollen mitochondria, enhanced Ca2+ overload, increased ROS production, and reduced mitochondrial respiration in Mfn2‐deficient cells. This view is based on a number of observations, namely, (a) Mfn2 KO or Mfn2‐silenced cells showed sustained PERK activation under basal conditions; (b) PERK silencing ameliorated the mitochondrial network and respiration and reduced ROS production and mitochondrial Ca2+ in Mfn2 KO cells; (c) PERK overexpression caused mitochondrial fragmentation and reduced ...

Proposed pathway for mitochondrial fission complex assembly. (1) Before fission complex assembly, the NH2-terminal arm of yeast Fis1p (indicated) interacts with

Our laboratory studies signal transduction systems controlled by heterotrimeric G proteins as well as Ras-related GTPases. The superfamily of GTPases control numerous signaling cascades based upon the regulated binding, hydrolysis, and exchange of guanine nucleotides; GTPases bound to GTP are active in downstream signaling while those bound to GDP are inactive. Mutant GTPases with abnormal GDP/GTP cycling are implicated in numerous human diseases, including cancer. It is our desire to better understand the regulation of heterotrimeric G proteins and Ras-related GTPases at the molecular level with the ultimate goal of using this information to design therapies to correct abnormal signaling mediated by these proteins and thereby treat associated pathologies.. ...

A cytoplasmic protein that greatly enhances the guanosine triphosphatase (GTPase) activity of N-ras protein but does not affect the activity of oncogenic ras mutants has been recently described. This protein (GAP) is shown here to be ubiquitous in higher eukaryotes and to interact with H-ras as well as with N-ras proteins. To identify the region of ras p21 with which GAP interacts, 21 H-ras mutant proteins were purified and tested for their ability to undergo stimulation of GTPase activity by GAP. Mutations in nonessential regions of H-ras p21 as well as mutations in its carboxyl-terminal domain (residues 165-185) and purine binding region (residues 117 and 119) did not decrease the ability of the protein to respond to GAP. In addition, an antibody against the carboxyl-terminal domain did not block GAP activity, supporting the conclusion that GAP does not interact with this region. Transforming mutations at positions 12, 59, and 61 (the phosphoryl binding region) abolished GTPase stimulation by ...

Small guanosine triphosphatases (GTPases) have long been known to control the activities of downstream protein kinases. Some members of a rather new multidomain protein family contain not only a GTPase domain of the ROC (Ras of complex protein) subtype but also a protein kinase domain, and both domains seem to cooperate with each other in the same polypeptide. Data now show that the kinase activity of one of these ROCO proteins depends on whether guanosine diphosphate or guanosine triphosphate (GTP) is bound and that the activity is controlled by the adjacent GTPase, which suggests a novel mechanism of intrinsic control. This ROCO family member, leucine-rich repeat kinase 2 (LRRK2), is of special interest because mutations within both its protein kinase and its GTPase domains are associated with Parkinsons disease (PD). These mutations lead to abnormally enhanced protein kinase activity, which is believed to cause or at least contribute to neuronal damage. The crystal structure of the GTPase ...

An essential GTPase which binds GTP, GDP and ppGpp with moderate affinity (with a twofold preference for GDP over GTP), shows high guanine nucleotide exchange rate constants for both nucleotides, and has a relatively low GTP hydrolysis rate. Deletion of the 159 N-terminal residues makes a protein that is non-functional in vivo but which retains nucleotide binding and GTPase activity. Required for cell cycle progression from G1 to S phase and for DNA replication.

Loss of the interferon-γ-inducible regulatory immunity-related GTPase IRG, Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient . . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

PD mutations in the RocCOR domain of LRRK2 lead to a decrease in GTPase activity [23,25,43,44,56-58], although the affected residues are most often not directly located in the GTP/GDP-binding pocket [37,46]. Using the bacterial CtRoco as a model, we previously showed that the RocCOR domain needs to cycle between a dimeric and monomeric state during the GTPase reaction, where GTP binding induces monomerization while the protein re-dimerizes after GTP hydrolysis [36]. This mechanism thus predicts that either mutations that stabilize the dimer or that block the protein in a monomeric state would impair the GTPase reaction. We concomitantly showed that the L487A mutation (corresponding to the PD-associated mutation I1371V in LRRK2) leads to a decrease in GTP turnover and stabilizes the CtRoco dimer. In agreement with these findings and with our model, it was very recently reported that the R1441G/C/H and N1473H PD mutations decrease the GTPase activity of the Roc domain of LRRK2 by destabilizing or ...

An essential GTPase which binds GTP, GDP and possibly (p)ppGpp with moderate affinity, with high nucleotide exchange rates and a fairly low GTP hydrolysis rate. Plays a role in control of the cell cycle, stress response, ribosome biogenesis and in those bacteria that undergo differentiation, in morphogenesis control.

Introduction: DM increases the risk of developing cardiovascular disease, although the specific molecular mechanisms underlying DM are not well understood, perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. The mitofusin 2 is a important protein to mitochondrial fusion. Additionally, muscle mitochondrial metabolism is regulated by a group of morphogenesis machinery proteins which are important for mitochondrial fusion and fission events and also for their independent effects on bioenergetics. The exercise training is a strategy for reversing the effects of mitochondrial dysfunction trough the regulation of mitochondrial protein transcription and biogenegis. The aim of this study was to verify if endurance exercise increases the expression of Mitofusin 2 in cardiac myocytes in experimental diabetes. Male Wistar rats were divided into 4 groups: control (C:8), control trained (CT=8), diabetic (D=8), diabetic trained (DT=8). DM was induced by STZ ...

MX2 antibody (MX dynamin-like GTPase 2) for WB. Anti-MX2 pAb (GTX55158) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.

IGTP Campus Can Ruti Ctra de Can Ruti, Camí de les Escoles s/n 08916 Badalona Barcelona, Spain Tel. (+34) 934 978 655 · comunicacio(ELIMINAR)@igtp.cat © IGTP. All rights reserved ...

IGTP Campus Can Ruti Ctra de Can Ruti, Camí de les Escoles s/n 08916 Badalona Barcelona, Spain Tel. (+34) 934 978 655 · comunicacio(ELIMINAR)@igtp.cat © IGTP. All rights reserved ...

Rabbit Polyclonal Anti-Mitofusin 1 Antibody [HRP]. Mitochondrial Fusion Marker. Validated: WB, IHC, IHC-P. Tested Reactivity: Human, Mouse, Rat. 100% Guaranteed.

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ウサギ・ポリクローナル抗体 ab50843 交差種: Ms,Rat,Hu 適用: WB,IP,ICC/IF…Mitofusin 2抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。

ウサギ・ポリクローナル抗体 ab50843 交差種: Ms,Rat,Hu 適用: WB,IP,ICC/IF…Mitofusin 2抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。

Here we report the generation and functional characterization of mice that lack the mitochondrial fusion protein Mfn-1 in cardiac myocytes. Mice lacking Mfn-1 exhibited normal heart function, but the mitochondria within Mfn-1-deficient myocytes were small and spherical. These findings are in marked contrast to our previous analysis of Mfn-2-deficient myocytes that displayed larger mitochondria (50). Despite mitochondrial fragmentation, Mfn-1-deficient myocytes were protected from ROS-induced mitochondrial depolarization and cell death.. Why are mitochondria smaller in Mfn-1-deficient myocytes yet enlarged in myocytes that are deficient for Mfn-2? One possibility is that the degree of mitochondrial size is dependent on the relative levels of mitofusin GTPase activity within the cell. Earlier studies (26) comparing mitofusins have shown that the two homologs exhibit considerable differences in terms of binding and hydrolyzing GTP, where Mfn-1 has eightfold higher GTPase activity than Mfn-2. ...

The Gtr1 protein of Saccharomyces cerevisiae is a member of the RagA subfamily of the Ras-like small GTPase superfamily. Gtr1 has been implicated in various cellular processes. Particularly, the Switch regions in the GTPase domain of Gtr1 are essential for TORC1 activation and amino acid signaling. Therefore, knowledge about the biochemical activity of Gtr1 is required to understand its mode of action and regulation. By employing tryptophan fluorescence analysis and radioactive GTPase assays, we demonstrate that Gtr1 can adopt two distinct GDP- and GTP-bound conformations, and that it hydrolyses GTP much slower than Ras proteins. Using cysteine mutagenesis of Arginine-37 and Valine-67, residues at the Switch I and II regions, respectively, we show altered GTPase activity and associated conformational changes as compared to the wild type protein and the cysteine-less mutant. The extremely low intrinsic GTPase activity of Gtr1 implies requirement for interaction with activating proteins to support its

Septin proteins are necessary for cytokinesis in budding yeast and Drosophila and are thought to be the subunits of the yeast neck filaments. To test whether septins actually form filaments, an immunoaffinity approach was used to isolate a septin complex from Drosophila embryos. The purified complex is comprised of the three previously identified septin polypeptides Pnut, Sep2, and Sep1. Hydrodynamic and sequence data suggest that the complex is composed of a heterotrimer of homodimers. The complex copurifies with one molecule of bound guanine nucleotide per septin polypeptide. It binds and hydrolyzes exogenously added GTP. These observations together with conserved sequence motifs identify the septins as members of the GTPase superfamily. We discuss a model of filament structure and speculate as to how the filaments are organized within cells. ...

Mitochondria are remarkably dynamic organelles. Time-lapse microscopy of living cells reveals that mitochondria undergo constant migration and morphological changes (Bereiter-Hahn and Voth, 1994; Nunnari et al., 1997; Rizzuto et al., 1998). Even in cells with a seemingly stable network of mitochondrial tubules, there are frequent and continual cycles of mitochondrial fusion and fission, opposing processes that exist in equilibrium and serve to maintain the overall architecture of these organelles (Bereiter-Hahn and Voth, 1994; Nunnari et al., 1997).. In both yeast and flies, mitochondrial fusion is controlled by the nuclearly encoded mitochondrial transmembrane GTPase, fuzzy onions (Fzo).* In Drosophila, Fzo is specifically and transiently expressed in spermatids. Disruption of Fzo prevents developmentally regulated mitochondrial fusion in postmeiotic spermatids and results in male sterility (Hales and Fuller, 1997). In budding yeast, deletion of FZO1 disrupts the highly branched, tubular ...

The bacterial homologues of the signal recognition particle (SRP) and its receptor, the Ffh*4.5S RNA ribonucleoprotein complex and the FtsY protein, respectively, form a unique complex in which both Ffh and FtsY act as GTPase activating proteins for one another, resulting in the mutual stimulation of GTP hydrolysis by both proteins. Previous work showed that 4.5S RNA enhances the GTPase activity in the presence of both Ffh and FtsY, but it was not clear how this was accomplished. In this work, kinetic and thermodynamic analyses of the GTPase reactions of Ffh and FtsY have provided insights into the role of 4.5S RNA in the GTPase cycles of Ffh and FtsY. We found that 4.5S RNA accelerates the association between Ffh and FtsY 400-fold in their GTP-bound form, analogous to its 200-fold catalytic effect on Ffh*FtsY association previously observed with the GppNHp-bound form [Peluso, P., et al. (2000) Science 288, 1640-1643]. Further, Ffh-FtsY association is rate-limiting for the observed GTPase ...

The immunity-related GTPases (IRGs) participate in the category of large interferon-inducible GTPases and constitute a cell-autonomous resistance system needed for the control of vacuolar pathogens like in mice. to spontaneous activation from the effector IRG protein when induced by IFNγ. This activation provides cytotoxic consequences producing a serious lymphopenia macrophage flaws and failure from the adaptive disease fighting capability in virulence elements and genetic deviation in the IRG program between different mouse strains correlates with level of resistance and susceptibility to virulent strains. Launch The immunity-related GTPases (IRG proteins previously known as p47 GTPases) had been first referred to in the 1990s as genes highly induced by disease via interferon gamma (IFNγ) (also to a lesser degree by type I IFN) in mice (Boehm et al. 1998; Carlow et al. 1995; Wall and Gilly 1992; Lafuse et al. 1995; Sorace et al. 1995; Taylor et al. 1996). Targeted deletions pioneered by ...

Background The mitochondrial GTPase mitofusin-2 ( MFN2) gene encodes a mitochondrial membrane protein that can induce apoptosis of hepatocellular carcinoma (HCC) via the mitochondrial apoptotic...

Members of the evolutionary conserved class of mitochondrial Fzo-GTPases have been identified in yeast, C. elegans, Drosophila and human. Here, we described the expression and function of the generally expressed human homologue Mfn1. The human genome contains two different functional genes encoding members of the Fzo-GTPase family, Mfn1 and Mfn2, which differ in their expression patterns. Interestingly, Drosophila also has two differently expressed genes encoding Fzo-GTPase family members: the founding member of the family fzo and dmfn (Hales and Fuller, 1997; Hwa et al., 2002). The Drosophila fzo protein is expressed only at the end of male meiosis and in early spermatids, where it is required for a developmentally regulated, massive mitochondrial fusion event in differentiating male germ cells (Hales and Fuller, 1997). In contrast, the Drosophila dmfn gene is broadly expressed in many tissues and stages of development (Hwa et al., 2002), where it presumably is involved in maintaining the ...

FtsZ has a GTPase activity that is associated with assembly and required for the dynamics of FtsZ polymers (24). In this study, we have investigated the properties of FtsZ2 that can support cell division despite having a dramatically reduced GTPase activity. We found that FtsZ2 is unable to assemble in vitro; however, it copolymerized upon addition of FtsZ, provided FtsZ is above the critical concentration. This supports a model for cooperative assembly of FtsZ polymers. Significantly, the stability of the copolymers increased with increasing FtsZ2 incorporation, implying FtsZ2 polymers, if formed, would be stable. Since FtsZ2 can support viability, our results suggest that stable FtsZ filaments are able to function in cell division. This result has important implications for the role of the Z ring in cell division, because it argues that constriction of the Z ring can occur through forces acting on FtsZ filaments.. FtsZ2 was isolated as an allele of ftsZ that was resistant to the cell division ...

TY - JOUR. T1 - Rab GTPase regulation of bacteria and protozoa phagocytosis occurs through the modulation of phagocytic receptor surface expression. AU - Seixas, E.. AU - Escrevente, C.. AU - Seabra, M.C.. AU - Barral, D.C.. N1 - info:eu-repo/grantAgreement/FCT/3599-PPCDT/104622/PT# info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F34094%2F2006/PT# info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F78491%2F2011/PT# This work was supported by Fundacao para a Ciencia e a Tecnologia (FCT) I.P., Portugal through grant PTDC/SAU-MII/104622/2008 (to M.C.S. and D.C.B.); the FCT Investigator Program (IF/00501/2014/CP1252/CT0001, to D.C.B.); and FCT post-doctoral fellowships SFRH/BPD/34094/2006 (to E.S.) and SFRH/BPD/78491/2011 (to C.E.). PY - 2018/8/29. Y1 - 2018/8/29. N2 - Phagocytosis of invading microorganisms by professional phagocytic cells has a central role in innate immunity. However, several microorganisms developed strategies to subvert this process. Previously, we reported that bacteria and ...

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Septins are filament-forming proteins important for organizing the cortex of animal and fungal cells. In mammals, 13 septin paralogues were recently shown to assemble into core heterohexamer and heterooctamer complexes, which serve as building blocks for apolar filamentous structures that differ among cell types. To determine how tissue-specific septin paralogue expression may shape core heteromer repertoires and thereby modulate properties of septin filaments, we devised protocols to analyze native septin heteromers with distinct numbers of subunits. Our evidence based on genetically manipulated human cells supports and extends recent concepts of homology subgroup-restricted assembly into distinct categories of apolar heterohexamers and heterooctamers. We also identify a category of tetramers that have a subunit composition equivalent to an octameric building block. These atypical tetramers are prevalent in lymphocytes and neural tissues, in which octamers are abundant but hexamers are rare. ...

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AGAP4 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 4 ) Blocking Peptide (the C terminal of AGAP4)(100ug) - Read User Reviews, Features, Research Applications and get the Best Price/Quote

Both the sec6/8 complex and septin filaments have been implicated in directing vesicles and proteins to sites of active membrane addition in yeast. The rat brain sec6/8 complex coimmunoprecipitates with a filament composed of four mammalian septins, suggesting an interaction between these complexes. …

Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Filaments are assembled from asymmetrical heterotrimers, composed of SEPT2, SEPT6 and SEPT7 that associate head-to-head to form a hexameric unit. Within the trimer, directly interacts with SEPT6, while interaction with SEPT2 seems indirect. In the absence of SEPT6, forms homodimers. Interacts directly with CENPE and links CENPE to septin filaments composed of SEPT2, SEPT6 and SEPT7. Interacts with SEPT5 and SEPT8 (By similarity). Interacts with SEPT9 and SEPT11. Component of a septin core octomeric complex consisting of SEPT12, SEPT7, SEPT6 and SEPT2 or SEPT4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12 and located in the sperm annulus; the SEPT12:SEPT7 association is mediated by the respective GTP-binding domains (PubMed:25588830 ...

Sigma-Aldrich offers abstracts and full-text articles by [Yongsheng Jia, Liyan Zhou, Chen Tian, Yehui Shi, Chen Wang, Zhongsheng Tong].

Ras-homologous (Rho) GTPases are involved in the regulation of a variety of cellular processes such as the organization of the actin cytoskeleton, malignant transformation and genotoxic stress-induced signaling. Here we show that, among the family of Rho GTPases, specifically rhoB mRNA expression is …

Immunity-related GTPase family M protein (IRGM), also known as interferon-inducible protein 1 (IFI1), is an enzyme that in humans is IRGM gene. IRGM is a member of the interferon-inducible GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens. Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohns disease and tuberculosis. GRCh38: Ensembl release 89: ENSG00000237693 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000069874 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: immunity-related GTPase family. Prescott NJ, Dominy KM, Kubo M, Lewis CM, Fisher SA, Redon R, Huang N, Stranger BE, Blaszczyk K, Hudspith B, Parkes G, Hosono N, Yamazaki K, Onnie CM, Forbes A, Dermitzakis ET, Nakamura Y, Mansfield JC, Sanderson J, Hurles ME, Roberts RG, Mathew CG (May 2010). Independent and population-specific ...

The protein encoded by this gene is a member of the Ras-related protein subfamily of the Ras GTPase superfamily. Members of this family are small GTPases that act as molecular switches to regulate cellular proliferation, differentiation, and apoptosis. This protein has been reported to activate in vitro transcriptional activity of the serum response element. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012 ...

3. Functional analysis of SEPTIN9 isoforms. Septins are a family of filament forming proteins. Septin filaments, which are referred to as the fourth part of the cytoskeleton, consist of repeats of heteromeric octamers. Several Septins, are associated with a variety of tumors. This is particularly true for Septin9, which surprisingly seem to have both proto-oncogenic and tumor suppressor function. This dualistic function might be connected to different SEPTIN9 isoforms that have been shown to differentially direct the association of Septin filaments with microtubules and acting filaments. We try to elucidate the impact of SEPTIN9 isoforms on the cellular localization and cell stability.. ...

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Genetic information processingProtein synthesistRNA and rRNA base modificationtRNA modification GTPase TrmE (TIGR00450; EC 3.6.-.-; HMM-score: 56.6) ...

Genetic information processingProtein synthesistRNA and rRNA base modificationtRNA modification GTPase TrmE (TIGR00450; EC 3.6.-.-; HMM-score: 56.6) ...

Dlp для активних субстанцій або комбінацій активних субстанцій з частотністю подання psur менше ніж 1 рік

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Autosomal dominant optic atrophy (adOA) is the most prevalent hereditary optic neuropathy with moderate to severe visual field loss and loss of retinal ganglion cells. The majority of cases of adOA...

Dear Editor: I read with interest the article by Dr. Cohn, et al regarding the natural history of autosomal dominant optic atrophy (DOA). The authors describe an average of 10-year follow up for 69 patients with genetically confirmed DOA. In their study, 6 (9%) patients enjoyed improvement in visual acuity by 2 or more lines. I found this surprising, and I wonder if the authors could provide further information regarding this group. Is it the opinion of the authors that these patients actually improved or that this may represent testing artifact or bias? Were they significantly younger than the rest of the cohort? Was their follow up significantly shorter? By how much did the acuities improve among this group? Was their baseline acuity more likely to come from outside records? Sincerely, Michael S Lee, MD ...

TY - JOUR. T1 - Autosomal dominant optic atrophy and cataract plus phenotype including axonal neuropathy. AU - Horga, Alejandro. AU - Bugiardini, Enrico. AU - Manole, Andreea. AU - Bremner, Fion. AU - Jaunmuktane, Zane. AU - Dankwa, Lois. AU - Rebelo, Adriana P.. AU - Woodward, Catherine E.. AU - Hargreaves, Iain P.. AU - Cortese, Andrea. AU - Pittman, Alan M.. AU - Brandner, Sebastian. AU - Polke, James M.. AU - Pitceathly, Robert D.S.. AU - Züchner, Stephan. AU - Hanna, Michael G.. AU - Scherer, Steven S.. AU - Houlden, Henry. AU - Reilly, Mary M.. N1 - Funding Information: The present study is not industry-sponsored. A. Horga, E. Bugiardini, and A. Manole report no disclosures. F. Bremner has received funding for travel or speaker honoraria from Allergan and has served on the Editorial Board for BMC Opthalmology, Frontiers in Neuro-opthalmology, and Tropical Medicine. Z. Jaunmuktane has served on the Editorial Board of Acta Neuropathologica. L. Dankwa, A.P. Rebelo, C.E. Woodward, and I. ...

Mutations in human and/or mouse homologs are associated with this disease. Synonyms: ADOAC; autosomal dominant optic atrophy 3; autosomal dominant optic atrophy and cataract; autosomal dominant optic atrophy type 3; OPA3; optic atrophy 3 with cataract

Autosomal dominant optic atrophy (OPA, MIM 165500) is an eye disease characterised by variable optic atrophy and reduction in visual acuity. It has an insidious onset in the first decade of life and is clinically highly heterogeneous. It is associated with a centrocecal scotoma of varying size and density and an acquired blue-yellow dyschromatopsia. Recent studies of three large Danish pedigrees have mapped a gene for dominant optic atrophy (OPA1) to a 10 cM region on chromosome 3q, between markers D3S1314 and D3S1265 (3q28-qter). Genetic linkage analysis in five British pedigrees confirms mapping to chromosome 3q28-qter. Haplotype analysis of a seven generation pedigree positions the disease causing gene between loci D3S3590 and D3S1305, corresponding to a genetic distance of 2 cM. This represents a significant linkage refinement and should facilitate positional cloning of the disease gene.. ...

Background Mutations in OPA3 have been reported in patients with autosomal dominant optic atrophy plus cataract and Costeff syndrome. Here, we report the results of a comprehensive study on OPA3 mutations, including the mutation spectrum and its prevalence in a large cohort of OPA1-negative autosomal dominant optic atrophy (ADOA) patients, the associated clinical phenotype and the functional characterisation of a newly identified OPA3 mutant. Methods Mutation analysis was carried out in a patient cohort of 121 independent ADOA patients. To characterise a novel OPA3 mutation, we analysed the mitochondrial import, steady-state levels and the mitochondrial localisation of the mutated protein in patients fibroblasts. Furthermore, the morphology of mitochondria harbouring the mutated OPA3 was monitored. Results We identified four independent cases (representing families with multiple affected members) with OPA3 mutations. Besides the known p.Q105E mutation, we observed a novel insertion, ...

Objective To assess phenotypic variation of affected individuals from British families with autosomal dominant optic atrophy. Design Eighty-seven patients from 21 families showing evidence of linkage to chromosome 3q were identified via the Genetic Clinic of Moorfields Eye Hospital, London, England. Genetic linkage analysis was carried out with markers from chromosome 3q28-qter. Patients underwent clinical examination and psychophysical and electrophysiological testing. Results Best-corrected visual acuity ranged from 20/20 (6/6 m) to light perception. Although visual acuity was not significantly worse in older patients in the group (χ2=3.20, df=4, P,.50), it did deteriorate with age in one third of the families. Subtle or temporal pallor of the optic disc occurred in 96 (55%) of 174 eyes and total atrophy in 76 (44%). Tritanopia was found in 6 (7.5%) of 80 patients; 65 (81.2%) had a mixed color deficit. A cecocentral scotoma was found in the vast majority. Peripheral motion detection threshold ...

Mourier et al. reveal that the mitochondrial fusion protein Mitofusin 2 (MFN2) is required to maintain production of the respiratory chain cofactor coenzyme Q.. The closely related GTPases MFN1 and MFN2 are both required for mitochondrial outer membrane fusion. Mfn1-deficient mice nevertheless seem perfectly healthy, but mice lacking Mfn2 die soon after birth. Moreover, only Mfn2 has been linked to human diseases, including the peripheral neuropathy Charcot-Marie-Tooth type 2A. Mourier et al. therefore investigated whether loss of Mfn2 affects mitochondrial function in other ways besides membrane fusion.. The researchers found that mitochondrial respiration and ATP production was impaired in Mfn2-deficient cardiomyocytes compared with wild-type and Mfn1-deficient cells. The levels and activities of individual respiratory chain protein complexes were unaltered in mitochondria lacking Mfn2, but the levels of coenzyme Q, an electron carrier that transfers electrons to respiratory chain complex III, ...

TY - JOUR. T1 - Drp1S600 phosphorylation regulates mitochondrial fission and progression of nephropathy in diabetic mice. AU - Galvan, Daniel L.. AU - Long, Jianyin. AU - Green, Nathanael. AU - Chang, Benny H.. AU - Lin, Jamie S.. AU - Schumacker, Paul. AU - Truong, Luan. AU - Overbeek, Paul. AU - Danesh, Farhad R.. PY - 2019. Y1 - 2019. N2 - Phosphorylation of dynamin-related protein 1 (Drp1) represents an important regulatory mechanism for mitochondrial fission. Here, we established the role of Drp1 serine 600 (Drp1S600) phosphorylation in mitochondrial fission in vivo and assessed the functional consequences of targeted elimination of the Drp1S600 phosphorylation site in the progression of diabetic nephropathy (DN). We generated a knockin mouse in which S600 was mutated to alanine (Drp1S600A). We found that diabetic Drp1S600A mice exhibited improved biochemical and histological features of DN along with reduced mitochondrial fission and diminished mitochondrial ROS in vivo. Importantly, we ...

The signal recognition particle and its receptor (SR) target nascent secretory proteins to the ER. SR is a heterodimeric ER membrane protein whose subunits, SRalpha and SRbeta, are both members of the GTPase superfamily. Here we characterize a 27-kD protein in Saccharomyces cerevisiae (encoded by SRP102) as a homologue of mammalian SRbeta. This notion is supported (a) by Srp102ps sequence similarity to SRbeta; (b) by its disposition as an ER membrane protein; (c) by its interaction with Srp101p, the yeast SRalpha homologue; and (d) by its role in SRP-dependent protein targeting in vivo. The GTP-binding site in Srp102p is surprisingly insensitive to single amino acid substitutions that inactivate other GTPases. Multiple mutations in the GTP-binding site, however, inactivate Srp102p. Loss of activity parallels a loss of affinity between Srp102p and Srp101p, indicating that the interaction between SR subunits is important for function. Deleting the transmembrane domain of Srp102p, the only known ...

Phosphorylation of dynamin-related protein 1 (Drp1) represents an important regulatory mechanism for mitochondrial fission. Here, we established the role of Drp1 serine 600 (Drp1S600) phosphorylation in mitochondrial fission in vivo and assessed the functional consequences of targeted elimination of the Drp1S600 phosphorylation site in the progression of diabetic nephropathy (DN). We generated a knockin mouse in which S600 was mutated to alanine (Drp1S600A). We found that diabetic Drp1S600A mice exhibited improved biochemical and histological features of DN along with reduced mitochondrial fission and diminished mitochondrial ROS in vivo. Importantly, we observed that the effect of Drp1S600 phosphorylation on mitochondrial fission in the diabetic milieu was stimulus dependent but not cell type dependent. Mechanistically, we show that mitochondrial fission in high-glucose conditions occurs through concomitant binding of phosphorylated Drp1S600 with mitochondrial fission factor (MFF) and ...

Phosphorylation of dynamin-related protein 1 (Drp1) represents an important regulatory mechanism for mitochondrial fission. Here, we established the role of Drp1 serine 600 (Drp1S600) phosphorylation in mitochondrial fission in vivo and assessed the functional consequences of targeted elimination of the Drp1S600 phosphorylation site in the progression of diabetic nephropathy (DN). We generated a knockin mouse in which S600 was mutated to alanine (Drp1S600A). We found that diabetic Drp1S600A mice exhibited improved biochemical and histological features of DN along with reduced mitochondrial fission and diminished mitochondrial ROS in vivo. Importantly, we observed that the effect of Drp1S600 phosphorylation on mitochondrial fission in the diabetic milieu was stimulus dependent but not cell type dependent. Mechanistically, we show that mitochondrial fission in high-glucose conditions occurs through concomitant binding of phosphorylated Drp1S600 with mitochondrial fission factor (MFF) and ...

Phosphorylation of dynamin-related protein 1 (Drp1) represents an important regulatory mechanism for mitochondrial fission. Here, we established the role of Drp1 serine 600 (Drp1S600) phosphorylation in mitochondrial fission in vivo and assessed the functional consequences of targeted elimination of the Drp1S600 phosphorylation site in the progression of diabetic nephropathy (DN). We generated a knockin mouse in which S600 was mutated to alanine (Drp1S600A). We found that diabetic Drp1S600A mice exhibited improved biochemical and histological features of DN along with reduced mitochondrial fission and diminished mitochondrial ROS in vivo. Importantly, we observed that the effect of Drp1S600 phosphorylation on mitochondrial fission in the diabetic milieu was stimulus dependent but not cell type dependent. Mechanistically, we show that mitochondrial fission in high-glucose conditions occurs through concomitant binding of phosphorylated Drp1S600 with mitochondrial fission factor (MFF) and ...

The ability of mice to resist infection with the protozoan parasite, Toxoplasma gondii, depends in large part on the function of members of a complex family of atypical large GTPases, the interferon-gamma-inducible immunity-related GTPases (IRG proteins). Nevertheless, some strains of T. gondii are highly virulent for mice because, as recently shown, they secrete a polymorphic protein kinase, ROP18, from the rhoptries into the host cell cytosol at the moment of cell invasion. Depending on the allele, ROP18 can act as a virulence factor for T. gondii by phosphorylating and thereby inactivating mouse IRG proteins. In this article we show that IRG proteins interact not only with ROP18, but also strongly with the products of another polymorphic locus, ROP5, already implicated as a major virulence factor from genetic crosses, but whose function has previously been a complete mystery. ROP5 proteins are members of the same protein family as ROP18 kinases but are pseudokinases by sequence, structure, ...

FOCAL POINT Two research teams probed how mitochondria engage fission-promoting, dynamin-related GTPases. In yeast cells, Mdv1 helps capture the GTPase Dnm1. (Top row) Janet Shaw (third from left), Sajjan Koirala (fourth from left), and colleagues determined the structure of the middle portion of Mdv1. Their structure (bottom left, from (1)) shows two Mdv1 molecules (green and purple) with their coils overlapping. (Middle row) Hidenori Otera (left), Chunxin Wang (right), and colleagues (not shown) found that human mitochondria rely on the protein Mff to capture the dynamin-related GTPase Drp1. The bottom row images (from (2)) show that overexpressing Mff breaks up mitochondrial networks (middle), but not when Drp1 is missing (right).. TOP ROW IMAGE COURTESY OF ERIC TAYLOR. MIDDLE ROW IMAGES COURTESTY OF HIDENORI OTERA (LEFT) AND YINGJIE WU (RIGHT).. ...

Fingerprint Dive into the research topics of Minireview: Mouse models of Rho GTPase function in mammary gland development, tumorigenesis, and metastasis. Together they form a unique fingerprint. ...

July 2019. Structural and functional studies reported this month in the journal Nature reveal the molecular basis of remodelling of the inner mitochondrial membrane by the protein complex Mgm1. Mitochondria are the powerhouses of our cells and play a fundamental role in human health. Balanced fusion and fission are essential for the proper function and physiology of these important organelles.. Mitochondria possess two membranes. In humans and animals remodelling of the inner mitochondrial membrane is mediated by a protein complex called OPA1. The related protein complex Mgm1 takes on this role in yeasts and other fungi. Both Mgm1 and OPA1 exist in mitochondria in two forms: a membrane-integrated long form and a short form that is soluble in the intermembrane space. Mutations in the OPA1 gene in humans are a common cause of autosomal dominant optic atrophy-a genetic disorder that affects the optic nerve. Mammalian cells that lack OPA1 and yeast strains that express temperature-sensitive versions ...

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Putative GTPase With A Role In Biogenesis Of RNA Pol II And PolIII; May Be Involved In Assembly Of RNA Polymerases II And III And In Their Transport Into The Nucleus; May Have A Role In Sister Chromatid Cohesion; Contains A Gly-Pro-Asn Motif In The G Domain; Similar To Npa3p And Gpn2p

As per a recent study, our body clock affects the immunity-related mechanism. This means that our health also depends on the bodys circadian rhythm along with other factors.

Niemann, H. H.; Knetsch, M. L. W.; Scherer, A.; Manstein, D. J.; Kull, F. J.: Crystal structure of a dynamin GTPase domain in both nucleotide-free and GDP-bound forms. The EMBO Journal 21 (21), pp. 5813 - 5821 (2001 ...

GAG genes participate in mitochondrial fission. A, Cells harboring GFP-labeled mitochondria and mutant for FZO1 alone (strain MYY2005) or together with either d

Mutants of FtsZ targeting the protofilament interface: effects on cell division and GTPase activity.s profile, publications, research topics, and co-authors

MTP18 is a mitochondrial protein and downstream target of the phosphatidylinositol 3-kinase (see PIK3CA, MIM 171834) signaling pathway that plays a role in cell viability and mitochondrial dynamics (Tondera et al., 2004 [PubMed 15155745]).[supplied by OMIM, Mar 2008 ...

Humans; Animals; Apoptosis; *Signal Transduction; GTP-Binding Proteins/*metabolism; rho GTP-Binding Proteins; GTP Phosphohydrolases/*metabolism. ...

Background GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. May act as a specific effector of RAP2A to...

ARHGAP25 GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB ...

Szabó, Aliz; Sümegi, Katalin; Fekete, Katalin; Hocsák, Enikő; Debreceni, Balázs; Sétáló, György (ifj.); Kovács, Krisztina; Deres, László; Kengyel, András Miklós; Kovács, Dominika; Mandl, József; Nyitrai, Miklós; Febbraio MA; Gallyas, Ferenc; Sümegi, Balázs ...

IGNOU MFN-02 Study Material is now available to download free of cost. No registration is required for downloading MFN-02 Study Material

Click on a genes description to view its network relationships with genes known to be involved in regulation of rab gtpase activity ...

Maybe TN isnt voting for any of the suspicious people (I mean that in the way of the top people that everyone is considering- Jan, Kai, myself and...