Spatiotemporal regulation of insulin signaling by liquid-liquid phase separation.

ABSTRACT: Insulin signals through its receptor to recruit insulin receptor substrates (IRS) and phosphatidylinositol 3-kinase (PI3K) to the plasma membrane for production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) from phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], which consequently activates protein kinase B (PKB). How insulin signals transduce from the plasma membrane into the cytoplasm is not clearly understood. Here we show that liquid-liquid phase separation (LLPS) plays a critical role in spatiotemporal control of insulin signaling through regulating multiple components including IRS1. Both protein concentration and insulin stimulation can drive the formation of intracellular IRS1 condensates through LLPS. Components including PI(4,5)P2, p85-PI3K and PDK1 are constitutively presen

SUBMITTER: Zhou K 

PROVIDER: S-EPMC9256590 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature