• Although each patient had different mutations, all had altered Golgi morphology and protein O-linked glycosylation that were rescued by overexpression of wild type PLA2G6. (bmj.com)
  • GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. (univ-lille.fr)
  • Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica. (univ-lille.fr)
  • Several mutations in the N terminus of the G-protein-coupled receptor rhodopsin disrupt NXS/T consensus sequences for N-linked glycosylation (located at N2 and N15) and cause sector retinitis pigmentosa in which the inferior retina preferentially degenerates. (jneurosci.org)
  • Mutations affecting glycosylation of the heptahelical G-protein-coupled receptor rhodopsin are associated with retinitis pigmentosa (RP), a disease characterized by progressive degeneration of photoreceptors. (jneurosci.org)
  • N-linked glycosylation is the most prevalent posttranslational modification of plasma membrane and secretory proteins and participates in many important biological roles such as protein folding, intracellular targeting, immune response, cell adhesion, and protease resistance. (jneurosci.org)
  • Both studies suggest that defects in rhodopsin glycosylation are associated with impairment of protein folding or stability. (jneurosci.org)
  • However, several recently developed technologies now allow one to systematically monitor the change of protein glycosylation and glycans in various biological fluids from a large number of individuals. (nih.gov)
  • Therefore, the goal of this Notice of Special Interest (NOSI) is to invite research projects using state-of-the-art methods of protein carbohydrate analyses to understand the potential impact of glycosylation on the etiology of AD and biomarker discovery. (nih.gov)
  • Consequences of aberrant glycosylation on the unfolded protein response and protein homeostasis. (nih.gov)
  • Affected individuals' fibroblasts, whose COG4 mRNA and protein were not decreased, exhibited delayed anterograde vesicular trafficking from the ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER. (zfin.org)
  • Over the next five years, our goals are to (1) identify novel recycling receptors required at different Golgi compartments and establish a systematic map of the intra-Golgi recycling network, (2) determine how the transmembrane receptors engage with their cargos, and (3) define the novel functions of a disease-associated membrane transporter in solute transport and protein recycling in the Golgi. (cornell.edu)
  • The golgins are a family of proteins, of which the protein encoded by this gene is a member, that are localized to the Golgi. (genetex.com)
  • This encoded protein has been postulated to play roles in the stacking of Golgi cisternae and in vesicular transport. (genetex.com)
  • This study establishes evidence of how altered cellular glycosylation enzyme expression impacts EV vesicle abundance and the protein content of EVs secreted from prostate cancer cells via dysregulation of the cell's endocytic pathway. (cancer.gov)
  • It also shows how differences in EV protein cargo, including glycosite occupancy and glycosylation patterns, may contribute to prostate carcinogenesis - making a case for EV-based diagnostics that incorporate glycosylation information for prostate cancer screening. (cancer.gov)
  • This gene encodes a Golgi protein which is a member of the polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-Ts) protein family. (nih.gov)
  • This information will be integrated with various biochemical approaches including metabolic inhibition of glycosylation and cell surface glycoengineering to custom-modify sLeX display to assess the extent to which sLeX presentation on a specific protein and/or lipid scaffold licenses E-selectin binding among blasts from various subtypes of human acute leukemias, and the impact of the relevant E-selectin receptor/ligand interaction(s) in leukemia cell biology. (cancer.gov)
  • Golgi satellites that formed during neuronal excitation were in close association with ER exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130. (janelia.org)
  • The enzyme encoded by this gene controls the initiation step of mucin-type O-linked protein glycosylation and transfer of N-acetylgalactosamine to serine and threonine amino acid residues. (nih.gov)
  • This protein may function as a follow-up enzyme in the initiation step of O-glycosylation. (nih.gov)
  • The folded structure gets transported via vesicles to the Golgi bodies (7). (chromatographyonline.com)
  • This process occurs predominantly in the ER, Golgi and secretory vesicles. (tocris.com)
  • Contributors examine how proteins translocate across the ER membrane, the processes that occur inside the ER lumen (e.g., folding, glycosylation, and disulfide bond formation), and how the proteins are packaged into vesicles and transported to the Golgi. (cshlpress.com)
  • COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. (univ-lille.fr)
  • Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. (univ-lille.fr)
  • The glycosylation machinery is responsible for assembling a diverse repertoire of glycan structures, collectively termed 'glycome', through the synchronized action of a portfolio of glycan-modifying enzymes including glycosyltransferases and glycosidases. (nature.com)
  • 2021. GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis . (ncbs.res.in)
  • In preliminary results, we have identified novel transmembrane components orchestrating recycling of specific subsets of Golgi enzymes. (cornell.edu)
  • Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites. (janelia.org)
  • This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants. (york.ac.uk)
  • We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis. (york.ac.uk)
  • My lab is interested in uncovering these fundamental mechanisms governing Golgi homeostasis using a multifaceted approach combining genetics, flow-cytometry, imaging, in vitro reconstitution, and proteomics. (cornell.edu)
  • The combined results of our experiments will elucidate how multiple recycling pathways sustain normal Golgi function, and how this homeostasis is disrupted in human disease. (cornell.edu)
  • H + and Pi Byproducts of Glycosylation Affect Ca 2+ Homeostasis and Are Retrieved from the Golgi Complex by Homologs of TMEM165 and XPR1. (bvsalud.org)
  • Unlike NKCC1, NKCC2 is minimally hybrid/complex N-glycosylated under basal conditions and yet it is trafficked to the plasma membrane region of hyper-osmotically challenged cells through mechanisms that require minimal complex N-glycosylation or functional Golgi cisternae. (elsevierpure.com)
  • Most plasma membrane proteins are sorted by the trans -Golgi network (TGN) in the conventional secretory pathway. (jneurosci.org)
  • Proline hydroxylation is catalyzed by membrane-anchored prolyl-4-hydroxylases (P4Hs) localized in ER and Golgi compartments. (elifesciences.org)
  • COP-I beta1 (green) staining at the Golgi (GM130, a cis-Golgi marker) (red), is redistributed out of the Golgi after EGF treatment of HeLa cells for 4 h. (cellimagelibrary.org)
  • Despite the importance of glycosylation and altered glycan structures in AD, the aberrant molecular and biochemical function of these glycosylated molecules to serve as disease modifiers remain largely elusive. (nih.gov)
  • Large-scale analysis of glycosylation in organisms includes glycomics (glycan profiling) and glycoproteomics (glycosylation site profiling) ( 5 ). (frontiersin.org)
  • Metabolic regulation of UDP-GlcNAc supply to Golgi N-glycan remodeling regulates glycoprotein affinities for galectins -and in turn, trafficking and presentation at the cell surface. (gr.jp)
  • The two N-glycosylation sites of PrP are variably PF 477736 utilized resulting in a mixture of di, mono and unglycosylated forms.7,8 This variability has important implications, in that the N-glycan pattern of PrPSc is characteristic of the different TSE and could be used as diagnostic marker.9 Furthermore, the signal sequence of PrP is inefficient in mediating translocation. (fabretp.org)
  • This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states. (york.ac.uk)
  • These glycoproteins are widely involved in important biological processes, such as antigen presentation, cytokine production and glycosylation progression. (frontiersin.org)
  • Glycosylation is an important post-translational modification of proteins, and glycoproteins are widely involved in various important cellular biological processes and diseases ( 1 ). (frontiersin.org)
  • The Golgi complex plays a prominent role in secretory and endocytic trafficking in eukaryotic cells and is key to the biosynthesis of glycoconjugates (glycoproteins and glycolipids) that are essential for life. (cornell.edu)
  • They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway, or on surface glycoproteins taken up from the endocytic pathway. (janelia.org)
  • Glycosylation is known to affect various cellular and physiological functions including regulation of enzymatic activities, cell differentiation and morphogenesis. (nih.gov)
  • Epub) Disrupted ER-to-Golgi trafficking underlies anti-HIV drugs and alcohol-induced cellular stress and hepatic injury. (genetex.com)
  • Dong is equally excited about what the work has to tell us about glycosylation - the attachment of sugars to large molecules like proteins and lipids. (childrenshospital.org)
  • GalNac-T1 staining (green) colocalizes with COP-I beta1 (red) staining at the Golgi (HPL) (gray) in unstimulated HeLa cells. (cellimagelibrary.org)
  • After EGF stimulation for 4 h, Helix Pomatia Lectin (HPL) (green) in HeLa cells expressing constitutively active mutant Arf1-GFP (Arf1(Q71L)-GFP) (gray) resists redistribution from Golgi (Giantin) (re. (cellimagelibrary.org)
  • V-ATPases also play a key role in a complex process called glycosylation, in which proteins are modified by adding sugar molecules. (medlineplus.gov)
  • Glycosylation and complex carbohydrates have been reported to play many critical roles in the early pathogenesis and progression of AD, but the potential of these molecules to serve as biomarkers and targets of disease intervention remains largely unexplored. (nih.gov)
  • The conserved oligomeric Golgi (COG) complex is involved in intracellular vesicular transport, and is composed of eight subunits distributed in two lobes, lobe A (COG1-4) and lobe B (COG5-8). (zfin.org)
  • Golgi resident proteins, such as glycosyltransferases and sugar nucleotide transporters, are precisely distributed across the Golgi stacks by recycling mechanisms that counteract the flow of ongoing vesicular transport. (cornell.edu)
  • Among the different CQAs (generally only a few for microbial products and more for mammalian products), a glycosylation profile of a product is well-recognized as a CQA that requires stringent monitoring and control. (chromatographyonline.com)
  • Although mutations T4K and T4N caused RD, N2S and T4V did not, demonstrating that glycosylation at N2 was not required for photoreceptor viability. (jneurosci.org)
  • In contrast, similar mutations eliminating glycosylation at N15 (N15S and T17M) caused rod death. (jneurosci.org)
  • Activation by subtilases including SBT3.8 in post-Golgi compartments depends on the N-terminal aspartate of the mature peptides. (elifesciences.org)
  • In this study we analyzed the Golgi and glycosylation in cultured skin fibroblasts in three patients with PLA2G6-associated neurodegeneration (PLAN). (bmj.com)
  • In addition, PrP polypeptide normally undergoes a variety of covalent modifications such as glycosylation, oxidation and GPI anchoring. (fabretp.org)
  • Golgi α-mannosidase II (GMII), a member of glycoside hydrolase family 38, cleaves two mannosyl residues from GlcNAcMan 5 GlcNAc 2 as part of the N-linked glycosylation pathway. (iastate.edu)
  • To elucidate the molecular and electronic details of the reaction mechanism, in particular the conformation of the substrate at the transition state, we performed quantum mechanics/molecular mechanics metadynamics simulations of the glycosylation reaction catalyzed by GMII. (iastate.edu)
  • Traditionally, it has been very difficult to study and monitor the alteration of glycosylation and glycans in relation to aging and early initiation of AD. (nih.gov)
  • To what extent differences in substrate specificity of HPATs may contribute to the selection of certain Hyp residues for glycosylation remains to be seen. (elifesciences.org)
  • The calculated free energy of activation for mannosyl glycosylation (23 kcal/mol) agrees very well with experiments, as does the conformation of the glycon mannosyl ring in the product of the glycosylation reaction (the covalent intermediate). (iastate.edu)
  • We show that formation of the single disulfide bonds competes with N-glycosylation and GPI addition. (fabretp.org)
  • SBT6.1-mediated cleavage within the variable domain allows for continued passage of the partially processed precursors through the secretory pathway, and for subsequent post-translational modifications including tyrosine sulfation and proline hydroxylation within, and proteolytic maturation after exit from the Golgi. (elifesciences.org)
  • Proline hydroxylation is a prerequisite for subsequent glycosylation. (elifesciences.org)
  • This altered steady-state equilibrium led to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks. (zfin.org)
  • Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of ER morphology and function, as well as its interactions with the nucleus, Golgi, and mitochondria. (cshlpress.com)
  • Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. (genetex.com)
  • Now, they've set their sights on Shiga and ricin toxins, and not only identified new potential lines of defense, but also shed new light on a fundamental part of cell biology: glycosylation. (childrenshospital.org)
  • Here we examined the role of rhodopsin glycosylation in biosynthesis, trafficking, and retinal degeneration (RD) using transgenic Xenopus laevis expressing glycosylation-defective human rhodopsin mutants. (jneurosci.org)
  • Thus, glycosylation was not crucial for rhodopsin biosynthesis or trafficking. (jneurosci.org)
  • Together, the human disease and animal models suggest that glycosylation plays a crucial role in the structure and/or function of rhodopsin. (jneurosci.org)
  • However, a clear role for rhodopsin glycosylation has not been established in vivo . (jneurosci.org)
  • Rather, nonglycosylated rhodopsin exhibited reduced ability to activate transducin, which was specifically associated with loss of glycosylation at N15. (jneurosci.org)
  • Further studies suggest that rhodopsin requires glycosylation for incorporation into ROS membranes. (jneurosci.org)
  • Cilium trafficking of P/rds was sustained even when the Golgi functions, including trans -Golgi-mediated conventional secretion, were inhibited by the small molecules brefeldin A, 30N12, and monensin. (jneurosci.org)
  • Glycosylation is a post-translational modification in which a sugar (or carbohydrate) is attached to a hydroxyl or other functional group of a macro molecule (such as DNA, lipids and proteins). (nih.gov)
  • Although one typically thinks of carbohydrates as associated with cell growth and viability, glycosylation also has an integral role in many processes leading to cell death. (nature.com)
  • This instalment reviews the various process parameters and raw material attributes that affect glycosylation, as well as the different analytical tools that are used for characterization, with greater emphasis on the chromatographic methods of analysis. (chromatographyonline.com)
  • Mass spectrum-based high-throughput characterization of glycosylation as well as proteomic analysis has been used for years ( 7 - 11 ). (frontiersin.org)
  • In ciliated cells, including bovine and Xenopus laevis rod photoreceptors, P/rds was robustly sensitive to endoglycosidase H, which is consistent with its bypassing the medial Golgi and traversing the unconventional secretory pathway. (jneurosci.org)
  • Researchers suspect that changes in V-ATPase function may disrupt the normal glycosylation of proteins, including several that are involved in the assembly and maintenance of elastic fibers. (medlineplus.gov)
  • Glycosylation of classical death receptors fine-tunes cell death programs. (nature.com)
  • Expression of T17M was more toxic than T4K to transgenic photoreceptors, further suggesting that glycosylation at N15 plays a more important physiological role than glycosylation at N2. (jneurosci.org)
  • We will identify the pertinent sLeX-bearing glycoconjugates among the different types of human leu- kemia cells, measure the ability of such glycoconjugates to engage E-selectin, and determine how expression of Golgi GTs shape creation of sLeX modifications among the different E-selectin ligands. (cancer.gov)
  • Localized in the Golgi, α (1,6) fucosyltranferase (FUT8), a glycotransferase responsible for catalyzing the addition of fucose onto glycoprotein, has been previously shown to have a role in cell motility and invasiveness, and its over expression has been shown to associated with AG prostate cancer. (cancer.gov)
  • Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth. (nih.gov)
  • 11 (1) : 23489 Flavivirus infections induce a Golgi stress response in vertebrate and mosquito cells. (genetex.com)
  • Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells. (york.ac.uk)
  • May be involved in O-glycosylation in kidney. (nih.gov)