Journal
JOURNAL OF CELL SCIENCE
Volume 135, Issue 1, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258584
Keywords
Insulin signalling; Insulin receptor; Insulin receptor substrate-1; Adipocyte; Insulin resistance
Categories
Funding
- Japan Society for the Promotion of Science (KAKENHI) [16K11479, 19K10054, 17K11649, 20H03854]
- Grants-in-Aid for Scientific Research [16K11479, 17K11649, 19K10054, 20H03854] Funding Source: KAKEN
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PRIP facilitates insulin signaling by modulating the internalization of insulin receptor (IR) in adipocytes, playing an important regulatory role in insulin signaling.
Insulin signalling is tightly controlled by various factors, but the exact molecular mechanism remains incompletely understood. We have previously reported that phospholipase C-related but catalytically inactive protein (PRIP; used here to refer to both PRIP-1 and PRIP-2, also known as PLCL1 and PLCL2, respectively) interacts with Akt1, the central molecule in insulin signalling. Here, we investigated whether PRIP is involved in the regulation of insulin signalling in adipocytes. We found that insulin signalling, including insulin-stimulated phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt, and glucose uptake were impaired in adipocytes from PRIP double-knockout (PRIP-KO) mice compared with those from wild-type (WT) mice. The amount of IR expressed on the cell surface was decreased in PRIP-KO adipocytes. Immunoprecipitation assays showed that PRIP interacted with IR. The reduced cell surface IR in PRIP-KO adipocytes was comparable with that in WT cells when Rab5 (Rab5a, -5b and -5c) expression was silenced using specific siRNA. In contrast, the dephosphorylation of IRS-1 at serine residues, some of which have been reported to be involved in the internalisation of IR, was impaired in cells from PRIP-KO mice. These results suggest that PRIP facilitates insulin signalling by modulating the internalisation of IR in adipocytes.
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