Phosphatidylinositol 4,5-Bisphosphate Homeostasis Regulated by Nir2 and Nir3 Proteins at Endoplasmic Reticulum-Plasma Membrane Junctions.

ABSTRACT: Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) at the plasma membrane (PM) constitutively controls many cellular functions, and its hydrolysis via receptor stimulation governs cell signaling. The PI transfer protein Nir2 is essential for replenishing PM PIP2 following receptor-induced hydrolysis, but key mechanistic aspects of this process remain elusive. Here, we demonstrate that PI at the membrane of the endoplasmic reticulum (ER) is required for the rapid replenishment of PM PIP2 mediated by Nir2. Nir2 detects PIP2 hydrolysis and translocates to ER-PM junctions via binding to phosphatidic acid. With distinct phosphatidic acid binding abilities and PI transfer protein activities, Nir2 and its homolog Nir3 differentially regulate PIP2 homeostasis in cells during intense receptor stimul

SUBMITTER: Chang CL 

PROVIDER: S-EPMC4505499 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature