In the present study, we made several key observations on how dynamin-mediated synaptic vesicle endocytosis contributes to neurotransmission by taking advantage of dynasore, a reversible small molecule inhibitor of dynamin function. First, in agreement with previous reports, we verified that dynasore is a bona fide and potent inhibitor of the GTPase activity of dynamin (Macia et al., 2006; Kirchhausen et al., 2008). This inhibition of dynamin function, in turn, was correlated with a marked suppression of synaptic vesicle endocytosis during and after synaptic stimulation. Second, dynasore, at concentrations that potently inhibits dynamin activation as well as synaptic vesicle endocytosis, caused use-dependent depression of evoked synaptic transmission at an extremely rapid timescale (∼1 s). This finding indicates that neurotransmission during repetitive stimulation requires rapid reuse of synaptic vesicles endocytosed in a dynamin-dependent manner (Pyle et al., 2000; Sara et al., 2002; Harata ...
Involvement of Dynamin-Related Protein 1 in Free Fatty Acid-Induced INS-1-Derived Cell Apoptosis. . 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.
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Sigma-Aldrich offers abstracts and full-text articles by [Yongsheng Jia, Liyan Zhou, Chen Tian, Yehui Shi, Chen Wang, Zhongsheng Tong].
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Dynamin GTPase activity increases when it oligomerizes either into helices in the presence of lipid templates or into rings in the presence of SH3 domain proteins. Dynasore is a dynamin inhibitor of moderate potency (IC50 similar to 15 mu M in vitro). We show that dynasore binds stoichiometrically to detergents used for in vitro drug screening, drastically reducing its potency (IC50 = 479 mu M) and research tool utility. We synthesized a focused set of dihydroxyl and trihydroxyl dynasore analogs called the Dyngo (TM) compounds, five of which had improved potency, reduced detergent binding and reduced cytotoxicity, conferred by changes in the position and/or number of hydroxyl substituents. The Dyngo compound 4a was the most potent compound, exhibiting a 37-fold improvement in potency over dynasore for liposome-stimulated helical dynamin activity. In contrast, while dynasore about equally inhibited dynamin assembled in its helical or ring states, 4a and 6a exhibited >36-fold reduced activity ...
Dynamin is an atypical multidomain GTPase containing a large GTPase domain, which is well known for its critical role in budding or scission of transport vesicles (Schmid & Frolov, 2011; Ferguson & De Camilli, 2012). Distinct from other GTPases, previous biochemical studies and recent structural analyses showed that its GTPase catalytic activity is stimulated by oligomerization, which requires the involvement of the middle domain and the GED domain, where the GED domain serves as an intramolecular GAP to regulate its GTPase activity (Chappie et al, 2011; Faelber et al, 2011). However, how dynamin GTPase activity is regulated in cells is unclear. Although many Src homology 3 domain‐containing proteins, such as Grb2 and SNX9, stimulate dynamin GTPase activity, they are not GAPs because they increase GTPase activity indirectly via modulating the oligomerization of dynamin by interacting with its proline‐rich domain (PRD) (Gout et al, 1993). So far, the only intermolecular GAP that has been ...
Backues, S.K. and Bednarek, S.Y. (2010). Arabidopsis Dynamin-Related Protein 1A polymers bind, but do not tubulate, liposomes. Biochem. Biophys. Res. Commun. 393, 734-739 [PDF]. Konopka, C. A. and Bednarek, S. Y. (2008). Comparison of the Dynamics and Functional Redundancy of the Arabidopsis Dynamin-Related Isoforms DRP1A and DRP1C during Plant Development. Plant Physiol. 147, 1590-1602. [PDF]. Konopka, C. A., Backues, S. K. and Bednarek, S. Y. (2008). Dynamics of Arabidopsis Dynamin-Related Protein 1C and a Clathrin Light Chain at the Plasma Membrane. Plant Cell 20, 1363-1380. [PDF]. Park, S., Rancour, D.M., and Bednarek, S.Y. (2008). In Planta analysis of the cell cycle-dependent localization of AtCDC48A and its critical roles in cell division, expansion and differentiation. Plant Phys. 148, 246-258 [PDF]. Park, S., Rancour, D.M., and Bednarek, S.Y. (2007). Protein domain-domain interactions and requirements for the negative regulation of Arabidopsis CDC48/P97 by the Plant Ubiquitin Regulatory ...
5−10 fold). Only pthaladyn-23 (dynamin I IC50 17.4 ± 5.8 μM) was an effective inhibitor of dynamin I mediated synaptic vesicle endocytosis in brain synaptosomes with an IC50 of 12.9 ± 5.9 μM. This compound was also competitive with respect to Mg2+·GTP. Thus the pthaladyns are the first GTP competitive inhibitors of dynamin I and II GTPase and may be effective new tools for the study of neuronal endocytosis.. ...
Eps15 homology domain (EHD) proteins are conserved adenosine triphosphatases that are involved in membrane remodeling. EHD family members are structurally similar to the guanosine triphosphatase (GTPase) dynamin, and both are essential for the fission step of clathrin-mediated endocytosis. This Journal Club highlights a recent study by Jakobsson et al. that reports the unexpected finding that, rather than having a redundant function, EHD can regulate dynamin activity. Dynamin helices assemble around the neck of budding endocytic vesicles; as dynamin helices lengthen, the neck of the growing bud may become so long that GTP hydrolysis is no longer sufficient to promote fission. EHD increases the efficiency of dynamin-induced fission by restricting the length of dynamin helices. Furthermore, EHD is able to bind both dynamin and amphiphysin. Therefore, we propose a model whereby amphiphysin recruits both EHD and dynamin in neurons to regulate clathrin-dependent synaptic vesicle endocytosis.. ...
Buy Dynasore (CAS 304448-55-3), a cell-permeable dynamin inhibitor cited in 18 publications. Join researchers using high quality Dynasore from Abcam and…
The generation and maintenance of correct lumen size and shape is essential for the function of tubular organs. Now, Monn Monn Myat and co-workers report that p21-activated kinase (Pak1) plays a novel role during lumen formation in Drosophila embryonic salivary glands (see p. 4177). The researchers show that Pak1 regulates the size and elongation of the apical domain of individual epithelial cells in the developing gland by decreasing and increasing E-cadherin levels at adherens junctions and basolateral membranes, respectively. Pak1 mediates these effects, they report, through Rab5- and Dynamin-dependent endocytosis of E-cadherin. Moreover, constitutively active Pak1 induces the formation of multiple intercellular lumens in the gland, an effect that is dependent on Rab5 and Dynamin, and on the Pak1 substrate Merlin. Together, these results identify a crucial role for Pak1 and E-cadherin endocytosis in lumen size and shape determination in fly salivary glands, and highlight a mechanism for ...
The studies described here establish Dnm1p as an important regulator of mitochondrial morphology in yeast. In dnm1 mutants, the mitochondrial membranes fail to be distributed properly at the cortex and collapse to one side of the cell. In contrast, the loss of Dnm1p function has no apparent effect on the morphology and distribution of other cytoplasmic organelles, including nuclei, the endoplasmic reticulum, the Golgi apparatus, and vacuoles. Despite their unusual morphology, dnm1 mitochondria are able to generate a membrane potential and import a Cox4-GFP marker protein into the mitochondrial matrix, suggesting that basic organelle functions are not severely impaired. Unlike other yeast mitochondrial morphology mutants, which rapidly lose mtDNA and exhibit defects in mitochondrial inheritance (Hermann and Shaw, 1998), dnm1 mitochondria retain their mtDNA and are efficiently transported into buds during division. Together, our results indicate that Dnm1p plays a very specific role in defining ...
Mitochondrial fission and fusion proteins are highly expressed in myocardium. However, mitochondrial fission and fusion are rare, and mitochondrial networks are absent, in adult cardiomyocytes, obviating a need for morphometric mitochondrial remodeling. The critical role of mitochondrial dynamics factors in hearts, therefore, remains to be determined. In this issue of Circulation Research, Ikeda et al describe a central function for the mitochondrial fission protein, Dynamin-related protein 1 (Drp-1), in macroautophagy and mitochondrial autophagy. Together with two other recent reports that cardiac-specific deletion of Drp1 perturbs mitophagy, these findings point to modulation of targeted mitochondrial elimination as a major quality control function for Drp1, and possibly other mitochondrial dynamism factors, in the heart.. Article, see p 264. Conventional wisdom is that mitochondria continuously undergo cyclic fission and fusion, collectively termed mitochondrial dynamism. Although observable ...
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 ...
Live imaging of mitochondria with fluorescent probes unraveled their restless shape restyling all along cell life. Chopping and reconstructing of mitochondrial membranes was soon attributed to large GTPases of the dynamin family and appeared to accompany crucial pathways, from the distribution of mitochondria to daughter cells during cell division, to making release of proapoptotic molecules from mitochondria easier during programmed cell death. Recently, fusion and fission events were shown to apply to other subcellular organelles, including peroxisomes. In addition, proteins modeling mitochondrial morphology were observed on other organelles. A single shared shaping machinery appears to be suitable to the coordination of relevant pathways involving different organelles. Here, we describe our recent discovery of the involvement of the fission protein Drp1 in shaping morphology of the endoplasmic reticulum: morphological defects impinge on ER performances, in particular the ability of the cell ...
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The results of this study indicate that NOSTRIN interacts directly with the M3R and is required for its correct spatial localization at the plasma membrane in aortic endothelial cells. In the absence of NOSTRIN, the function of the M3R was markedly impaired, resulting in abolition of the calcium response to acetylcholine, an impaired activation of eNOS, and the inhibition of vascular relaxation. These changes at the cellular level were reflected in vivo in the existence of elevated blood pressure and diastolic dysfunction in NOSTRINΔEC mice.. The interaction of NOSTRIN with the M3R is to our knowledge the first example of an F-BAR protein interacting with a Gαq/11-protein-coupled receptor. The interaction is direct and involves the SH3 domain of NOSTRIN. The SH3 domain alone was not sufficient to bind to the M3R, indicating that additional motifs in NOSTRIN might be required. On the side of the M3R, the interaction with NOSTRIN involved the i3loop, which comprises 240 amino acids but contains ...
Basagiannis D, Zografou S, Galanopoulou K, Christoforidis S. (2017) Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner. Sci Rep....
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Dynamin, which is encoded by three genes in mammals, is a GTPase implicated in endocytic membrane fission. Dynamin 1 and 3 are predominantly expressed in brain, while dynamin 2 is ubiquitously expressed. With the goal of assessing the impact of the lack of dynamin on cell physiology, we previously generated and characterized dynamin 1 and 2 double KO (DKO) fibroblasts. These DKO cells were unexpectedly viable in spite of a severe impairment of clathrin-mediated endocytosis. As low-level expression of the dynamin 3 gene in these cells could not be excluded, we have now engineered dynamin 1, 2, and 3 triple KO (TKO) fibroblasts. These cells did not reveal any additional defects beyond what was previously observed in DKO fibroblasts. Surprisingly, while fluid phase endocytosis and peripheral membrane ruffling were not impaired by the lack of all three dynamins, two structurally similar, widely used dynamin inhibitors, dynasore and Dyngo-4a, robustly inhibited these two processes both in wild type ...
Link to Pubmed [PMID] - 24970086. Science 2014 Jun;344(6191):1510-5. Dynamin superfamily molecular motors use guanosine triphosphate (GTP) as a source of energy for membrane-remodeling events. We found that knockdown of nucleoside diphosphate kinases (NDPKs) NM23-H1/H2, which produce GTP through adenosine triphosphate (ATP)-driven conversion of guanosine diphosphate (GDP), inhibited dynamin-mediated endocytosis. NM23-H1/H2 localized at clathrin-coated pits and interacted with the proline-rich domain of dynamin. In vitro, NM23-H1/H2 were recruited to dynamin-induced tubules, stimulated GTP-loading on dynamin, and triggered fission in the presence of ATP and GDP. NM23-H4, a mitochondria-specific NDPK, colocalized with mitochondrial dynamin-like OPA1 involved in mitochondria inner membrane fusion and increased GTP-loading on OPA1. Like OPA1 loss of function, silencing of NM23-H4 but not NM23-H1/H2 resulted in mitochondrial fragmentation, reflecting fusion defects. Thus, NDPKs interact with and ...
Dynamin is a large GTPase with a relative molecular mass of 96,000 (Mr 96K) that is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Although its function is apparently essential for scission of newly formed vesicles from the plasma membrane, the nature of dynamins role in the scission process is still unclear. It has been proposed that dynamin is a regulator (similar to classical G proteins) of downstream effectors. Here we report the analysis of several point mutants of dynamins GTPase effector (GED) and GTPase domains. We show that oligomerization and GTP binding alone, by dynamin, are not sufficient for endocytosis in vivo. Rather, efficient GTP hydrolysis and an associated conformational change are also required. These data argue that dynamin has a mechanochemical function in vesicle scission.
Rabbit polyclonal to Dynamin-1.Dynamins represent one of the subfamilies of GTP-binding proteins.These proteins share considerable sequence similarity over the N-terminal portion of the molecule, which contains the GTPase domain.Dynamins are associated with microtubules.. black individuals from the prior research had been lost to check out up. Three brand-new alloHSCT recipients had been enrolled. We contacted five entitled alloHSCT recipients to sign up the three brand-new alloHSCT SDZ 220-581 Ammonium salt individuals. HSCT and matched-control individuals had been enrolled more than a 15-month period. The matched-control and alloHSCT characteristics are summarized in Desk 1. All individuals had been Caucasian. AlloHSCT was connected with postponed maturation. Elevation Z-scores had been markedly low in alloHSCT individuals while BMI Z-scores didnt differ considerably. AlloHSCT sitting elevation relative to elevation was considerably lower in comparison to handles (p ...
Methamphetamine (METH) is an addictive drug that can cause toxicity and degeneration in the brain. Several pieces of evidence have demonstrated that METH toxicity results in increases in oxidative stress that regulate an intracellular signaling cascade that leads to cell death. Recently, several studies have emphasized that the overload of cytosolic calcium levels and mitochondrial fission into a small mitochondrial structure is involved in cell death processes. In the present study, we aimed to investigate the effects of METH toxicity on cytosolic calcium overload and mitochondrial fission in neuroblastoma SH-SY5Y cells. Additionally, the protective effect of melatonin against METH-induced toxicity was also investigated. The results of the present study demonstrated that METH significantly decreases cell viability and increases the levels of mitochondrial fission (Fis1 and Drp1) proteins and pro-apoptotic protein, Bax in isolated mitochondria. The levels of Drp1 in the cytosol of METH-treated cells had
Mitochondrial division is important for mitochondrial distribution and function. Recent data have demonstrated that ER-mitochondria contacts mark mitochondrial division sites, but the molecular basis and functions of these contacts are not understood. Here we show that in yeast, the ER-mitochondria tethering complex, ERMES, and the highly conserved Miro GTPase, Gem1, are spatially and functionally linked to ER-associated mitochondrial division. Gem1 acts as a negative regulator of ER-mitochondria contacts, an activity required for the spatial resolution and distribution of newly generated mitochondrial tips following division. Previous data have demonstrated that ERMES localizes with a subset of actively replicating mitochondrial nucleoids. We show that mitochondrial division is spatially linked to nucleoids and that a majority of these nucleoids segregate prior to division, resulting in their distribution into newly generated tips in the mitochondrial network. Thus, we postulate that ...
Mitochondria are highly dynamic organelles that constantly undergo fission and fusion events to adapt to changes in the cellular environment. Aberrant mitochondrial fission has been associated with several types of cardiovascular dysfunction; inhibition of pathologically aberrant mitochondrial fission has been shown to be cardioprotective. Pathological fission is mediated by the excessive activation of GTPase dynamin-related protein 1 (Drp1), making it an attractive therapeutic target in numerous cardiovascular diseases. Mitochondrial division inhibitor (mdivi-1) is widely used small molecule reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate injury. The purpose of our study was to understand the pleiotropic effects of mdivi-1 on mitochondrial dynamics, mitochondrial respiration, electron transport activities, and macro-autophagy. In this study, we found that mdivi-1 treatment decreased Drp1 expression, proteolytically cleaved L-OPA1, and altered the expression of ...
Background: Mitochondrial fission is the dynamic process by which mitochondria are cleaved and fragmented. Recent reports suggest that pharmacologic inhibition of fission attenuates lethal ischemia-reperfusion (I-R) injury, thereby implying that fission contributes to cell death. However, the molecular mechanisms by which fission regulates cell fate are unresolved.. Hypothesis: We propose that: (i) I-R elicits the translocation of DRP1 (dynamin-related protein 1: a critical mediator of fission) from the cytosol to the mitochondria. Once in position, DRP1 will constrict the mitochondria, thereby (ii) facilitating release of Cytochrome C (Cyto C) into the cytosol and (iii) triggering apoptosis. If so, (iv) inhibition of DRP1 translocation will attenuate Cyto C release and offer cytoprotection.. Methods: In Protocol 1, cultured HL-1 cells underwent 2 h simulated I + 5, 30 or 120 min reoxygenation or a matched normoxic period. For each group, subcellular localization of DRP1 and Cyto C was resolved ...
Veden ODS by m lo po dat b val ho prezidenta V clava Klause o n vrat do strany, ekl iDNES.cz poslanec Boris astn . S Klausem u dlouho mluv o jeho mo n m pod lu na z chran esk pravice a ODS. Ur it jsem m l v dy z jeho postoj pocit, e m z jem pomoci, e ho situace v ODS velmi tr p , uvedl astn .
diabetes OR diabetic Exclude a word using the minus sign. Virchow -triad Use Parentheses. water AND (cup OR glass) Add an asterisk (*) at end of a word to include word stems. Neuro* will search for Neurology, Neuroscientist, Neurological, and so on Use quotes to search for an exact phrase. "primary prevention of cancer ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
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This material is supplemental to Peter et al., BAR Domains as Sensors of Membrane Curvature: The Amphiphysin BAR Structure Science Express Nov 26 (abstract); print version Jan 23, 2004. Please click on one of the pictures or links below to view the corresponding data.. ...
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Dynamin 1 is a neuron-specific guanosine triphosphatase thought to be critically required for the fission reaction of synaptic vesicle endocytosis. Unexpectedly, mice lacking dynamin 1 were able to form functional synapses, even though their postnatal viability was limited. However, during spontaneous network activity, branched, tubular plasma membrane invaginations accumulated, capped by clathrin-coated pits, in synapses of dynamin 1-knockout mice. Synaptic vesicle endocytosis was severely impaired during strong exogenous stimulation but resumed efficiently when the stimulus was terminated. Thus, dynamin 1-independent mechanisms can support limited synaptic vesicle endocytosis, but dynamin 1 is needed during high levels of neuronal activity.
TY - JOUR. T1 - Dynamic changes of mitochondrial fusion and fission proteins after transient cerebral ischemia in mice. AU - Liu, Wentao. AU - Tian, Fengfeng. AU - Kurata, Tomoko. AU - Morimoto, Nobutoshi. AU - Abe, Koji. PY - 2012/6/1. Y1 - 2012/6/1. N2 - With fusion or fission, mitochondria alter their morphology in response to various physiological and pathological stimuli, resulting in elongated, tubular, interconnected, or fragmented forms. Immunohistochemistry and Western blot analysis were performed at 2 days, 7 days, 14 days, and 28 days after 90 min of transient middle cerebral artery occlusion (tMCAO) in mice. This study showed that mitochondrial fission protein dynamin-related protein 1 (Drp1) and fusion protein optic atrophy 1 (Opa1) were both upregulated in the ischemic penumbra, with the peak at 2 days after tMCAO, whereas phosphorylated-Drp1 (P-Drp1) progressively increased with a peak at 14 days after tMCAO. Double-immunofluorescence analysis showed many Drp1/cytochrome c oxidase ...
Androgen and androgen receptors (AR) play critical roles in the proliferation of prostate cancer through transcriptional regulation of target genes. Here, we found that androgens upregulated the expression of dynamin-related protein 1 (Drp1), which is involved in the induction of mitochondrial fission, a common event in mitosis and apoptosis. Clinical tissue samples and various prostate cancer cell lines revealed a positive correlation between Drp1 and AR levels. Treatment of androgen-sensitive cells with an AR agonist, R1881, and antagonist, bicalutamide, showed that Drp1 is transcriptionally regulated by androgens, as confirmed by an AR ChIP-seq assay. Live imaging experiments using pAcGFP1-Mito stably transfected LNCaP (mito-green) cells revealed that androgen did not induce significant mitochondrial fission by itself, although Drp1 was upregulated. However, when treated with CGP37157 (CGP), an inhibitor of mitochondrial Ca²⁺ efflux, these cells exhibited mitochondrial fission, which was further
Endocytosis is an essential phenomenon in eukaryotic cells. In animal cells, dynamin and clathrin play central roles in vesicle formation in the process of endocytosis, but the roles of similar proteins in plants are less well understood. Here, we observed the localization pattern and behavior of GFP-labeled ,i,Arabidopsis,/i, dynamin-related proteins (DRP1A and DRP2B), and clathrin light chain (AtCLC) around the plasma membrane in tobacco suspension cells by using variable incidence angle fluorescence microscopy (VIAFM). GFP fusions of DRP1A, DRP2B and AtCLC were observed as dot-like puncta 200-500 nm in diameter. The puncta moved to and away from the cell surface or also assembled and disassembled. The localization pattern and behavior of the puncta were similar to those of animal dynamin and clathrin signals reported previously. These results raise the possibility that DRP1A, DRP2B and AtCLC are involved in membrane trafficking around the plasma membrane, including endocytosis.. ...
Dynamin 1. The big surprise of the E2 publication is the DNM1 gene coding for Dynamin 1. This small GTPase is involved in severing synaptic vesicles from the plasma membrane (please watch this cartoon on endocytosis.org). Basically, synaptic vesicles constantly merge with the plasma membrane during neuronal firing. In order to recycle vesicles, they are coated with a protein called clathrin. Dynamins then act as the twine that finally severs the recycled vesicle from the synaptic membrane. How this process leads to seizures is still poorly understood. However, we can assume that we are dealing with a process that affects the development of synapses over time. Some patients with DNM1 mutations seem to have intractable epilepsy and a highly active EEG. Figure 2 shows the EEG of a patient with a DNM1 mutation with constant slow-spike wave, the electrographic hallmark of Lennox-Gastaut Syndrome. In total, we identifed 5 patients with de novo DNM1 mutations, accounting for almost 2% of patients with ...
We recently identified dynamin as a third nucleotide-sensitive microtubule-associated protein in brain tissue, in addition to kinesin and cytoplasmic dynein. Molecular cloning analysis has revealed that dynamin contains the three consensus elements characteristic of GTP-binding proteins, and biochemical results support a role for GTP in dynamin function. Dynamin is also homologous to the Mx proteins, involved in interferon-induced viral resistance, and the product of the yeast VPS1 gene, involved in vacuolar protein sorting. These results identify a novel class of GTP-utilizing proteins, with apparently diverse functions. ...
TY - JOUR. T1 - Nanoparticle‐Mediated Delivery of Mitochondrial Division Inhibitor 1 to the Myocardium Protects the Heart From Ischemia‐Reperfusion Injury Through Inhibition of Mitochondria Outer Membrane Permeabilization. T2 - A New Therapeutic Modality for Acute Myocardial Infarction. AU - Ishikita, Ayako. AU - Matoba, Tetsuya. AU - Ikeda, Gentaro. AU - Koga, Jun Ichiro. AU - Nakano, Kaku. AU - Sadoshima, Junichi. AU - Egashira, Kensuke. PY - 2016/7/22. Y1 - 2016/7/22. N2 - BackgroundMitochondria‐mediated cell death plays a critical role in myocardial ischemia‐reperfusion (IR) injury. We hypothesized that nanoparticle‐mediated drug delivery of mitochondrial division inhibitor 1 (Mdivi1) protects hearts from IR injury through inhibition of mitochondria outer membrane permeabilization (MOMP), which causes mitochondrial‐mediated cell death.Methods and ResultsWe formulated poly (lactic‐co‐glycolic acid) nanoparticles containing Mdivi1 (Mdivi1‐NP). We recently demonstrated that ...
How does dynamin oligomerise? Research on the mechanism of dynamin in vesicle scission and endocytosis. Research on proteins involved in clathrin-coated vesicle formation. Research on membrane bending. Research on protein-lipid interactions. Research on vesicle trafficking pathways. As a group we investigate vesicle budding using a variety of structural and functional approaches.
An influx of calcium into neurons causes mitochondrial fission, according to Han et al.. To respond to changing cellular needs, mitochondria move, fuse together, or undergo fission. Han et al. now reveal some of the proteins and signals that regulate fission in neurons.. The authors tested mitochondrial responses to an increase in potassium (K+) levels, which mimics an action potential. The K+ spike brought mitochondria to a halt and prompted their division, making them shorter and rounder. These changes depended on the opening of voltage-dependent calcium channels and the resulting Ca2+ gradient, which in turn activates the Ca2+/calmodulin-dependent protein kinase (CaMKIα). A CaMKIα antagonist blocked K+-triggered changes in mitochondrial shape.. In their search for CaMKIα substrates, the authors turned to Drp1 (dynamin-related protein 1), which promotes mitochondrial fission and whose sequence suggested it could be phosphorylated. And the authors found that it was, in fact, a CaMKIα ...
Mutations in the PTEN-induced novel kinase 1 (Pink1) gene cause a recessive form of early onset parkinsonism, and all the evidence points to mitochondria as the prime locus of the damage. From its first identification, Pink1 was found to be important at keeping a healthy electrical balance across the mitochondrial membrane (see ARF related news story and Valente et al., 2004). Further studies in fruit flies showed that Pink1 knockout results in severe swelling and disorganization of mitochondria. These morphological effects were attributed to a lack of normal mitochondrial fission, as expression of the fission-promoting GTPase dynamin-related protein 1 (Drp1) compensated for the loss of Pink1 (see Park et al., 2006; Clark et al., 2006; and ARF related news story on Yang et al., 2008 and ARF related news story on Poole et al., 2008).. But data are accumulating in support of the controversial idea that the target for Pink1s attack may lie elsewhere, that is, not in mitochondrial fission/fusion ...