Phospholipase C-related but catalytically inactive protein acts as a positive regulator of insulin signalling in adipocytes

Jing Gao, Akiko Mizokami, Hiroshi Takeuchi, Aonan Li, Fei Huang, Haruki Nagano, Takashi Kanematsu, Eijiro Jimi, Masato Hirata

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numberjcs.258584
JournalJournal of cell science
Volume135
Issue number1
DOIs
Publication statusPublished - Jan 2022

All Science Journal Classification (ASJC) codes

  • Cell Biology

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