p24 family type 1 transmembrane proteins are required for insulin biosynthesis and secretion in pancreatic beta-cells.
The p24 protein family have multiple functions in protein transport in the early secretory pathway. In this study we examined the role of p24 proteins in insulin transport. Several members were detected in insulinoma cell lines and rat islets and expression levels positively correlated with insulin abundance, particularly for p24delta1 and p24beta1. Knocking down p24delta1 in insulinoma cell lines, which also resulted in the concomitant knock-down of other family members, impaired glucose-stimulated insulin secretion, decreased total cellular insulin content and reduced proinsulin biosynthesis. There was no effect on overall protein biosynthesis or ER stress. These results suggest that p24delta1 and possibly other p24 family proteins are required for normal insulin biosynthesis and subsequent secretion in pancreatic beta-cells.
Zhang
Liling
L
Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Volchuk
Allen
A
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D011384:Proinsulin / Q000096:biosynthesis; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar
D002352:Carrier Proteins; D006728:Hormones; D007328:Insulin; D008565:Membrane Proteins; D011384:Proinsulin; D005947:Glucose