Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The guanosine triphosphatase Rab1 regulates the transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi apparatus through interaction with effector molecules, but the molecular mechanisms by which this occurs are unknown. Here, the tethering factor p115 was shown to be a Rab1 effector that binds directly to activated Rab1. Rab1 recruited p115 to coat protein complex II (COPII) vesicles during budding from the endoplasmic reticulum, where it interacted with a select set of COPII vesicle-associated SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) to form a cis-SNARE complex that promotes targeting to the Golgi apparatus. We propose that Rab1-regulated assembly of functional effector-SNARE complexes defines a conserved molecular mechanism to coordinate recognition between subcellular compartments.
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PMID:Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. 1093 51

In mammals, coat complex II (COPII)-coated transport vesicles deliver secretory cargo to vesicular tubular clusters (VTCs) that facilitate cargo sorting and transport to the Golgi. We documented in vitro tethering and SNARE-dependent homotypic fusion of endoplasmic reticulum-derived COPII transport vesicles to form larger cargo containers characteristic of VTCs ( Xu, D., and Hay, J. C. (2004) J. Cell Biol. 167, 997-1003). COPII vesicles thus appear to contain all necessary components for homotypic tethering and fusion, providing a pathway for de novo VTC biogenesis. Here we demonstrate that antibodies against the endoplasmic reticulum/Golgi SNARE Syntaxin 5 inhibit COPII vesicle homotypic tethering as well as fusion, implying an unanticipated role for SNAREs upstream of fusion. Inhibition of SNARE complex access and/or disassembly with dominant-negative alpha-soluble NSF attachment protein (SNAP) also inhibited tethering, implicating SNARE status as a critical determinant in COPII vesicle tethering. The tethering-defective vesicles generated in the presence of dominant-negative alpha-SNAP specifically lacked the Rab1 effectors p115 and GM130 but not other peripheral membrane proteins. Furthermore, Rab effectors, including p115, were shown to be required for homotypic COPII vesicle tethering. Thus, our results demonstrate a requirement for SNARE-dependent tether recruitment and function in COPII vesicle fusion. We anticipate that recruitment of tether molecules by an upstream SNARE signal ensures that tethering events are initiated only at focal sites containing appropriately poised fusion machinery.
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PMID:SNARE status regulates tether recruitment and function in homotypic COPII vesicle fusion. 1703 14

Docosahexaenoic acid [DHA, 22:6(n-3)] is enriched in brain membrane phospholipids and is important to brain development and function through its influence on neurite outgrowth and neurotransmitter secretion. Fusion of intracellular vesicles with the plasma membrane involving SNARE [soluble N-ethylmaleimide-sensitive fusion (NSF) protein attachment protein receptor] protein assembly, membrane fusion, and then disassembly are events common in membrane extension and neurotransmitter release. We determined whether feeding an (n-3) fatty acid-deficient diet, known to reduce brain phospholipid DHA, alters SNARE protein and SNARE complex expression or protein nitrosylation in the hippocampus of rats. Female rats were fed diets with 1.3 or 0.02% energy (n-3) alpha-linolenic acid from 2 wk before gestation then throughout gestation and lactation (n = 8/diet), and the male offspring were weaned to the maternal diet. Hippocampus phospholipid fatty acids and SNARE proteins were determined in male offspring at 90 d of age. Hippocampus phospholipid DHA was lower and (n-6) docosapentaenoic acid [DPA, 22:5(n-6)] was higher in the (n-3) fatty acid-deficient rats compared with the control group (P < 0.05). Multiplex Western blots using antibodies to syntaxin, synaptosome-associated protein of 25kDa (SNAP-25), and complexin II, showed higher ternary SNARE complexes but no differences in syntaxin, SNAP-25, or complex II expression in hippocampus of the (n-3) fatty acid-deficient rats compared with the control group (P < 0.05). S-nitrosylation of syntaxin was also significantly lower in the (n-3) fatty acid-deficient rats than in the control group. These studies suggest that altered SNARE complex binding or disassembly could be important in explaining the diverse cellular events associated with altered tissue DHA.
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PMID:Dietary polyunsaturated fat that is low in (n-3) and high in (n-6) fatty acids alters the SNARE protein complex and nitrosylation in rat hippocampus. 1763 54

Atg18p and Atg21p are two highly homologous yeast autophagy proteins. Atg18p functions in both autophagy and the selective Cvt-pathway, while the function of Atg21p is restricted to the Cvt-pathway. The yeast genome encodes with Ygr223cp (Hsv2p), a third member of this protein family. So far no function has been assigned to Ygr223cp. By colocalization with the endosomal marker Snf7-RFP and an RFP-tagged FYVE domain, we here identify the localization of a pool of Atg18p, Atg21p and Ygr223cp at endosomes. Endosomal recruitment of all three proteins depends on PtdIns3P generated by the Vps34-complex II containing Vps38p, but not on the function of the Vps34-complex I. Since only the Vps34-complex I is essential for autophagy, we expect that at endosomes Atg18p, Atg21p and Ygr223cp have a function distinct from autophagy. Some Vps Class D mutants involved in Golgi-to-endosome transport are required for the endosomal recruitment of GFP-Atg18p, -Atg21p and -Ygr223cp. These include the Qa-SNARE Pep12p, its SM protein Vps45p, the Rab GTPase Vps21p and the Rab effector Vac1p. Deletion of ATG18, ATG21 and YGR223c, alone or simultaneously has no obvious function on the MVB-pathway and CPY-sorting. However, overexpression of ATG21 leads to CPY secretion. We further show, to our knowledge for the first time, that Ygr223cp affects an autophagic process, namely micronucleophagy.
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PMID:Dissecting the localization and function of Atg18, Atg21 and Ygr223c. 1876 50

Upon starvation, Grh1, a peripheral membrane protein located at endoplasmic reticulum (ER) exit sites and early Golgi in Saccharomyces cerevisiae under growth conditions, relocates to a compartment called compartment for unconventional protein secretion (CUPS). Here we report that CUPS lack Golgi enzymes, but contain the coat protein complex II (COPII) vesicle tethering protein Uso1 and the Golgi t-SNARE Sed5. Interestingly, CUPS biogenesis is independent of COPII- and COPI-mediated membrane transport. Pik1- and Sec7-mediated membrane export from the late Golgi is required for complete assembly of CUPS, and Vps34 is needed for their maintenance. CUPS formation is triggered by glucose, but not nitrogen starvation. Moreover, upon return to growth conditions, CUPS are absorbed into the ER, and not the vacuole. Altogether our findings indicate that CUPS are not specialized autophagosomes as suggested previously. We suggest that starvation triggers relocation of secretory and endosomal membranes, but not their enzymes, to generate CUPS to sort and secrete proteins that do not enter, or are not processed by enzymes of the ER-Golgi pathway of secretion.
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PMID:Remodeling of secretory compartments creates CUPS during nutrient starvation. 2551 90