PMID- 23396488
OWN - NLM
STAT- MEDLINE
DCOM- 20131112
LR  - 20221207
IS  - 1460-2423 (Electronic)
IS  - 0959-6658 (Print)
IS  - 0959-6658 (Linking)
VI  - 23
IP  - 6
DP  - 2013 Jun
TI  - A non-enzymatic function of Golgi glycosyltransferases: mediation of Golgi 
      fragmentation by interaction with non-muscle myosin IIA.
PG  - 690-708
LID - 10.1093/glycob/cwt009 [doi]
AB  - 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 (beta-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 
      beta-galactoside alpha2,3 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 beta-COP KD or 
      BFA treatment. This is a novel non-enzymatic function of Golgi 
      glycosyltransferases.
FAU - Petrosyan, Armen
AU  - Petrosyan A
AD  - Department of Research Service, VA Nebraska-Western Iowa Health Care System, 
      Omaha, NE 68105 USA.
FAU - Cheng, Pi-Wan
AU  - Cheng PW
LA  - eng
GR  - 1R21HL097238/HL/NHLBI NIH HHS/United States
GR  - 2R01HL48282/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130207
PL  - England
TA  - Glycobiology
JT  - Glycobiology
JID - 9104124
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Coatomer Protein)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (KNK 437)
RN  - 0 (MYH9 protein, human)
RN  - 0 (Molecular Motor Proteins)
RN  - 0 (Pyrrolidinones)
RN  - 11089-65-9 (Tunicamycin)
RN  - 20350-15-6 (Brefeldin A)
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.102 (beta-1,3-galactosyl-O-glycosyl-glycoprotein 
      beta-1,6-N-acetylglucosaminyltransferase 3)
RN  - EC 2.4.99.- (Sialyltransferases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
RN  - EC 2.4.99.4 (beta-Galactoside alpha-2,3-Sialyltransferase)
RN  - EC 2.4.99.4 (ST3GAL1 protein, human)
SB  - IM
MH  - Benzhydryl Compounds/pharmacology
MH  - Brefeldin A/pharmacology
MH  - Coatomer Protein/genetics/metabolism
MH  - Endoplasmic Reticulum/drug effects/enzymology
MH  - Golgi Apparatus/drug effects/*enzymology
MH  - HEK293 Cells
MH  - HT29 Cells
MH  - Heat-Shock Proteins/antagonists & inhibitors
MH  - Humans
MH  - Molecular Motor Proteins/*metabolism
MH  - Myosin Heavy Chains/*metabolism
MH  - N-Acetylglucosaminyltransferases/*physiology
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Binding
MH  - Proteolysis
MH  - Pyrrolidinones/pharmacology
MH  - Sialyltransferases/metabolism
MH  - Tunicamycin/pharmacology
MH  - beta-Galactoside alpha-2,3-Sialyltransferase
PMC - PMC3641799
OTO - NOTNLM
OT  - brefeldin A
OT  - glycosyltransferase
OT  - non-muscle myosin IIA
OT  - restoration of fragmented Golgi in cancer cells to a compact phenotype
OT  - stress-induced Golgi fragmentation
EDAT- 2013/02/12 06:00
MHDA- 2013/11/13 06:00
PMCR- 2014/06/01
CRDT- 2013/02/12 06:00
PHST- 2013/02/12 06:00 [entrez]
PHST- 2013/02/12 06:00 [pubmed]
PHST- 2013/11/13 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - cwt009 [pii]
AID - 10.1093/glycob/cwt009 [doi]
PST - ppublish
SO  - Glycobiology. 2013 Jun;23(6):690-708. doi: 10.1093/glycob/cwt009. Epub 2013 Feb 
      7.