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  • complexes
  • The review begins with an article by Federica Brandizzi that provides the necessary molecular background on coat protein complexes in relation to the so-called secretory units model for ER-Golgi transport in highly vacuolated plant cells. (plantphysiol.org)
  • Eukaryotic cells have evolved a highly conserved ER quality control system that catalyzes protein folding and prevents unfolded polypeptides or unassembled protein complexes from reaching their final destinations (for review see Ellgaard and Helenius, 2001 ). (rupress.org)
  • Structural studies are revealing the mechanisms by which SNARES form complexes and interact with other proteins. (biologists.org)
  • The broad range of cellular functions for p97 is thought to derive from its ability to unfold proteins or disassemble protein complexes, but the detailed mechanism of how p97 works and is linked to specific cellular processes remains largely unknown. (pnas.org)
  • Dissection of the degradation process revealed that upon release from calnexin, extensively oxidized BACE457 transiently entered in disulfide-bonded complexes associated with the lumenal chaperones BiP and protein disulfide isomerase (PDI) before unfolding and dislocation into the cytosol for degradation. (rupress.org)
  • BACE457 and its lumenal variant accumulated in disulfide-bonded complexes, in the ER lumen, also when protein degradation was inhibited. (rupress.org)
  • We report the unexpected transient formation of covalent complexes in the ER lumen during the ERAD process, and we show that PDI participates as an oxidoreductase and a redox-driven chaperone in the preparation of proteins for degradation from the mammalian ER. (rupress.org)
  • These include the design of monomeric proteins for increased stability and complexes for increased binding affinity. (jove.com)
  • lipids
  • Exchange of lipids, metabolites or proteins across the lipid bilayer can occur through integral membrane proteins - as demonstrated for peroxisomes, mitochondria or chloroplasts. (biologists.org)
  • In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. (einj.org)
  • Among these, the secretion and uptake of molecular contents, including proteins, lipids, metabolites, and nucleic acids, from adjacent or remote cells is an efficient system that modulates cellular homeostasis and adaptation. (einj.org)
  • Glycosylation is a major form of post-translational modification and plays various important roles in organisms by modifying proteins or lipids, which generates functional variability and can increase their stability. (iospress.com)
  • Glycosylation is a post-translational modification where sugars (monosaccharides) or sugar chains (oligosaccharides) are covalently bound to proteins or lipids. (iospress.com)
  • membranes
  • High-resolution images from replicas of quick-frozen, freeze-dried Golgi membranes reveal that Golgi incubated in vitro with unfractionated cytosol (Fig. 6 A) or reconstituted cytosol (not shown) exhibit abundant buds and vesicles with a punctate surface coating. (nih.gov)
  • Thus, GLUT proteins are intimately embedded in membranes, and the most highly conserved regions are the putative membrane-spanning domains that serve a common function, the creation of a pore for facilitative diffusion of monosaccharides. (diabetesincontrol.com)
  • Golgi
  • Like in vitro transport to the medial-Golgi (medial assay), transport to the trans-Golgi and TGN requires cytosol, ATP, and N-ethylmaleimide-sensitive fusion protein (NSF). (nih.gov)
  • Since we have modified that original procedure to retain additional factors required for transport to late Golgi compartments, we determined whether this ARF-depleted cytosol is also deficient in coated bud formation. (nih.gov)
  • Its products subsequently pass through the Golgi apparatus on the way to the cell surface (true secretion) or to the lytic compartment of the cell (vacuolar protein transport). (plantphysiol.org)
  • These characteristics are of great importance, especially because Golgi stacks in plants, along with their protein processing functions, have been termed polysaccharide factories and their activity is essential for formation of a cell wall during cytokinesis and growth. (plantphysiol.org)
  • A role for the vesicle tethering protein, p115, in the post-mitotic stacking of reassembling Golgi cisternae in a cell-free system. (nih.gov)
  • Golgi reassembly stacking protein 65 (GRASP65), an NEM-sensitive membrane-bound component, is required for the stacking process.Temporal analysis suggests that p115 plays a transient role in stacking that may be upstream of GRASP65-mediated stacking.These results implicate p115 and its receptors in the initial alignment and docking of single cisternae that may be an important prerequisite for stack formation. (nih.gov)
  • Golgi reassembly stacking protein 65 (GRASP65), an NEM-sensitive membrane-bound component, is required for the stacking process. (nih.gov)
  • NSF-mediated cisternal regrowth requires a vesicle tethering protein, p115, which we now show operates through its two Golgi receptors, GM130 and giantin. (nih.gov)
  • Since then, p97 has been shown to play a critical role in the degradation of misfolded membrane and secretory proteins ( 4 ) and has also been linked to a broad array of cellular processes, including Golgi membrane reassembly ( 5 ), membrane transport ( 6 ), regulation of myofibril assembly ( 7 ), cell division ( 8 ), formation of protein aggregates ( 9 ), and autophagosome maturation ( 10 , 11 ). (pnas.org)
  • Cdc48
  • p97/Cdc48 is similar to the NSF protein involved in vesicle fusion in the secretory pathway. (rupress.org)
  • p97/Cdc48 (in mammals also called VCP for valosin-containing protein) is an essential AAA-ATPase that participates in a wide variety of cellular pathways using distinct adapters and other cofactors ( Woodman, 2003 ). (rupress.org)
  • The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. (nih.gov)
  • Here we demonstrate that another member of this family, Cdc48 in yeast and p97 in mammals, is required for the export of ER proteins into the cytosol. (nih.gov)
  • Whereas Cdc48/p97 was previously known to function in a complex with the cofactor p47 (ref. 5) in membrane fusion, we demonstrate that its role in ER protein export requires the interacting partners Ufd1 and Npl4. (nih.gov)
  • We propose that the Cdc48/p97-Ufd1-Npl4 complex extracts proteins from the ER membrane for cytosolic degradation. (nih.gov)
  • The available temperature-sensitive (ts) mutants of yeast Cdc48 require long incubations to fully extinguish their activities, and the molecular bases for their effects are not known. (pnas.org)
  • cytosolic
  • For example, the US11 protein of the human cytomegalovirus targets the major histocompatibility complex class I heavy chain for cytosolic degradation. (nih.gov)
  • vitro
  • 1993). Deletion of both yeast thioredoxin genes obliterates LMA1 activity of the cytosol in vitro and causes a striking vacuole inheritance defect in vivo ( Xu and Wickner, 1996 ). (rupress.org)
  • receptor
  • The heavy chain is successively implicated in the toxin binding at the surface of the motoneurons, the internalization by dual-receptor-mediated endocytosis and the translocation of the light chain into the cytosol. (biomedcentral.com)
  • In addition to the GSV pool, GLUT4 also cycles through an early endosomal compartment in an endocytotic/exocytotic pathway (distinct from fluid-phase endocytosis) analogous to that described for other insulin-responsive proteins, such as the mannose-6-phosphate/insulin-like growth factor 2 receptor and the transferrin receptor. (diabetesincontrol.com)
  • degradation
  • Different strategies have been developed in the last decades to overcome endosomal accumulation and subsequent lysosomal degradation of targeted protein-based drugs. (mdpi.com)
  • Because of the physiological importance of glycosylation, defects in genes encoding proteins involved in glycosylation or glycan degradation are sometimes associated with human diseases. (iospress.com)
  • binds
  • In the majority of cases, the targeting moiety is an antibody [ 1 , 2 ] or antibody fragment [ 1 , 3 ] but equally it can also be another protein species or a non-protein chemical structure that recognizes and binds to a suitable target cell-specific surface molecule. (mdpi.com)
  • Here, we report that its cognate partner VAMP721, which assembles with SYP121 to drive membrane fusion, binds to the KAT1 K + channel via two sites on the protein, only one of which contributes to channel-gating control. (plantphysiol.org)
  • fusion proteins
  • In this review we summarize the various efforts made to establish efficient techniques to disrupt the endosomal membrane barrier including the use of molecular ferries such as cell penetrating peptides or viral membrane fusion proteins, endosomal leakage inducing molecules such as saponins or monensin and physicochemical methods as represented by photochemical internalization. (mdpi.com)
  • physiological
  • A thorough analysis of the physiological role of these modifications has been hampered by the lack of reagents that specifically recognize the phosphorylated states of these proteins. (jneurosci.org)
  • cleaves
  • BACE501 cleaves the amyloid precursor protein to initiate the processing pathway leading to the generation of the β-amyloid peptides deposited in the senile plaques associated with Alzheimer's disease ( Selkoe, 2001 ). (rupress.org)
  • late endosomes
  • Direct fusion between late endosomes and lysosomes was an N-ethylmaleimide-sensitive factor-dependent event and was inhibited by GDP-dissociation inhibitor, indicating a requirement for a rab protein.We suggest that in cells, delivery of endocytosed ligands to an organelle where proteolytic digestion occurs is mediated by direct fusion of late endosomes with lysosomes.The consequences of this fusion to the maintenance and function of lysosomes are discussed. (nih.gov)
  • Direct fusion between late endosomes and lysosomes was an N-ethylmaleimide-sensitive factor-dependent event and was inhibited by GDP-dissociation inhibitor, indicating a requirement for a rab protein. (nih.gov)
  • highly conserved
  • Thioredoxin is a ubiquitous small protein ( Holmgren, 1985 ) with a pair of cysteine within a highly conserved active site. (rupress.org)
  • This factor was identified as GRASP65, a highly conserved, N-myristoylated protein that exists as a tight complex with GM130 on the membrane (Barr et al. (nih.gov)
  • interact
  • Both IRGM and Stx17 directly interact with mammalian Atg8 proteins, thus being guided to autophagosomes. (rupress.org)
  • Whereas all UBX proteins interact with p97, only those containing a ubiquitin-associated domain associate with ubiquitin conjugates ( 19 ). (pnas.org)
  • polypeptides
  • The two ATPase domains (D1 and D2) of p97 appear to alternate in ATP hydrolysis, which is essential for the movement of polypeptides from the ER membrane into the cytosol. (rupress.org)
  • UniProt
  • p>When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later. (uniprot.org)
  • assay
  • The kinetics of transport to late compartments are slower, and less cytosol is needed for guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS) to inhibit transport, suggesting that each assay reconstitutes a distinct transport event. (nih.gov)
  • molecular
  • The molecular identification of genes encoding enzymes that catalyze steps in TAG biosynthesis from glycerol 3-phosphate has revealed an unexpected number of protein isoforms of the glycerol phosphate acyltransferase (GPAT), acylglycerolphosphate acyltransferase (AGPAT), and lipin (phosphatidate phosphatase) families that appear to catalyze similar biochemical reactions. (physiology.org)
  • Little is known about the molecular consequences of these phosphorylations, the way they effect protein-protein interactions, and how this translates into changes in synaptic function. (jneurosci.org)
  • inhibitors
  • p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors. (uniprot.org)
  • requirement for a rab
  • The requirement for Ca 2+ for fusion was a later event than the requirement for a rab protein since the system became resistant to inhibition by GDP dissociation inhibitor at earlier times than it became resistant to BAPTA. (rupress.org)
  • Liver
  • On the other hand, ABCB4 protein is mainly expressed in the liver, although low levels of ABCB4 mRNA expression are found in the adrenal gland, muscle, tonsil, spleen, placenta, testis, and ileum [ 4 ]. (hindawi.com)
  • subsequent
  • It is therefore in subsequent rounds of synaptic vesicle exocytosis that the activity-dependent stimulation of protein kinases and phosphatases becomes manifest. (jneurosci.org)
  • functional
  • Although this observation clearly suggests a very direct functional interaction between the three proteins, it does not provide an explanation for the role of VCIP135 in membrane fusion. (rupress.org)
  • Multiple glucose transporter genes have been identified [66,that encode a family of homologous proteins exhibiting different functional properties and marked differences in tissue-specific expression. (diabetesincontrol.com)