title: A non-enzymatic function of Golgi glycosyltransferases: mediation of Golgi fragmentation by interaction with non-muscle myosin IIA.
abstract: The Golgi apparatus undergoes morphological changes under stress or malignant transformation, but the precise mechanisms are not known. We recently showed that non-muscle myosin IIA (NMIIA) binds to the cytoplasmic tail of Core 2 N-acetylglucosaminyltransferase mucus-type (C2GnT-M) and transports it to the endoplasmic reticulum for recycling. Here, we report that Golgi fragmentation induced by brefeldin A (BFA) or coatomer protein (β-COP) knockdown (KD) in Panc1-bC2GnT-M (c-Myc) cells is accompanied by the increased association of NMIIA with C2GnT-M and its degradation by proteasomes. Golgi fragmentation is prevented by inhibition or KD of NMIIA. Using multiple approaches, we have shown that the speed of BFA-induced Golgi fragmentation is positively correlated with the levels of this enzyme in the Golgi. The observation is reproduced in LNCaP cells which express high levels of two endogenous glycosyltransferases--C2GnT-L and β-galactoside α2,3 sialyltransferase 1. NMIIA is found to form complexes with these two enzymes but not Golgi matrix proteins. The KD of both enzymes or the prevention of Golgi glycosyltransferases from exiting endoplasmic reticulum reduced Golgi-associated NMIIA and decreased the BFA-induced fragmentation. Interestingly, the fragmented Golgi detected in colon cancer HT-29 cells can be restored to a compact morphology after inhibition or KD of NMIIA. The Golgi disorganization induced by the microtubule or actin destructive agent is NMIIA-independent and does not affect the levels of glycosyltransferases. We conclude that NMIIA interacts with Golgi residential but not matrix proteins, and this interaction is responsible for Golgi fragmentation induced by β-COP KD or BFA treatment. This is a novel non-enzymatic function of Golgi glycosyltransferases.
authors: Department of Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105 USA.
authors: Armen
authors: A
authors: Petrosyan
authors: Pi-Wan
authors: PW
authors: Cheng
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D020756:Coatomer Protein / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D006056:Golgi Apparatus / Q000187:drug effects / Q000201:enzymology*; D057809:HEK293 Cells; D019073:HT29 Cells; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D020409:Molecular Motor Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D011760:Pyrrolidinones / Q000494:pharmacology; D012799:Sialyltransferases / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D001559:Benzhydryl Compounds; D020756:Coatomer Protein; D006360:Heat-Shock Proteins; C410027:KNK 437; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D011760:Pyrrolidinones; D014415:Tunicamycin; D020126:Brefeldin A; D017351:N-Acetylglucosaminyltransferases; C117361:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3; D012799:Sialyltransferases; D046988:Proteasome Endopeptidase Complex; D018995:Myosin Heavy Chains; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human
keywords: brefeldin A; glycosyltransferase; non-muscle myosin IIA; restoration of fragmented Golgi in cancer cells to a compact phenotype; stress-induced Golgi fragmentation
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