Positive contribution of ERdj5/JPDI to endoplasmic reticulum protein quality control in the salivary gland.
In eukaryotic cells, most membrane and secretory proteins are modified post-translationally in the ER (endoplasmic reticulum) for correct folding and assembly. Disulfide-bond formation is one of the important modifications affecting folding and is catalysed by the PDI (protein disulfide isomerase) family proteins. ERdj5 [also known as JPDI (J-domain-containing PDI-like protein)] is a member of the PDI family proteins and has been reported to act as a reductase in ERAD (ER-associated degradation). However, the role of ERdj5 at the whole-body level remains unclear. Therefore in the present study we generated ERdj5-knockout mice {the mouse gene of ERdj5 is known as Dnajc10 [DnaJ (Hsp40) homologue, subfamily C, member 10]} and analysed them. Although ERdj5-knockout mice were viable and healthy, the ER stress response was activated in the salivary gland of the knockout mice more than that of control mice. Furthermore, in ERdj5-knockout cells, the expression of exogenous ERdj5 mitigated the ER stress caused by overproduction of alpha-amylase, which is one of the most abundant proteins in saliva and has five intramolecular disulfide bonds. This effect was dependent on the thioredoxin-like motifs of ERdj5. Thus we suggest that ERdj5 contributes to ER protein quality control in the salivary gland.
Iwawaki Initiative Research Unit, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Akira
A
Hosoda
Mio
M
Tokuda
Ryoko
R
Akai
Kenji
K
Kohno
Takao
T
Iwawaki
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004220:Disulfides / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism* / Q000648:ultrastructure; D000516:alpha-Amylases / Q000378:metabolism
D004220:Disulfides; C530517:ERdj5 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; D000516:alpha-Amylases