A novel function of VCP (valosin-containing protein; p97) in the control of N-glycosylation of proteins in the endoplasmic reticulum.
alpha-Chain of T-cell receptor (TCR) is a typical ERAD (ER-associated degradation) substrate degraded in the absence of other TCR subunits. Depletion of derlin 1 fails to induce accumulation of alphaTCR despite inducing accumulation of alpha1-antitrypsin, another ERAD substrate. Furthermore, while depletion of VCP does not affect levels of alpha1-antitrypsin, it induces an increase in levels of alphaTCR. RNAi of VCP induces preferential accumulation of alphaTCR with less mannose residues, suggesting its retention within the ER. Mass spectrometric analysis of cellular N-linked glycans revealed that depletion of VCP decreases the level of high-mannose glycoproteins, increases the levels of truncated low-mannose glycoproteins and induces changes in the abundance of complex glycans assembled in post-ER compartments. Since proteasome inhibition was unable to mimic those changes, they cannot be regarded as a simple consequence of inhibited ERAD but represent a complex effect of VCP on the function of the ER.
Lass
Agnieszka
A
Department of Anatomy and Cell Biology, Indiana University School of Medicine-Evansville, Evansville, IN 47712, USA.
McConnell
Elizabeth
E
Nowis
Dominika
D
Mechref
Yehia
Y
Kang
Pilsoo
P
Novotny
Milos V
MV
Wójcik
Cezary
C
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008358:Mannose / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D014176:Protein Biosynthesis; D021381:Protein Transport; D034622:RNA Interference; D025801:Ubiquitin / Q000737:chemistry; D000074405:Valosin Containing Protein; D000515:alpha 1-Antitrypsin / Q000737:chemistry
D018797:Cell Cycle Proteins; C487709:DERL1 protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D025801:Ubiquitin; D000515:alpha 1-Antitrypsin; D049452:Green Fluorescent Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; D008358:Mannose