RASSF4 controls SOCE and ER-PM junctions through regulation of PI(4,5)P₂.

ABSTRACT: RAS association domain family 4 (RASSF4) is involved in tumorigenesis and regulation of the Hippo pathway. In this study, we identify new functional roles of RASSF4. First, we discovered that RASSF4 regulates store-operated Ca²⁺ entry (SOCE), a fundamental Ca²⁺ signaling mechanism, by affecting the translocation of the endoplasmic reticulum (ER) Ca²⁺ sensor stromal interaction molecule 1 (STIM1) to ER-plasma membrane (PM) junctions. It was further revealed that RASSF4 regulates the formation of ER-PM junctions and the ER-PM tethering function of extended synaptotagmins E-Syt2 and E-Syt3. Moreover, steady-state PM phosphatidylinositol 4,5-bisphosphate (PI[4,5]P₂) levels, important for localization of STIM1 and E-Syts at ER-PM junctions, were reduc

SUBMITTER: Chen YJ 

PROVIDER: S-EPMC5496610 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature