Unknown

Dataset Information

0

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 reduced in RASSF4-knockdown cells. Furthermore, we demonstrated that RASSF4 interacts with and regulates the activity of adenosine diphosphate ribosylation factor 6 (ARF6), a small G protein and upstream regulator of type I phosphatidylinositol phosphate kinases (PIP5Ks) and PM PI(4,5)P2 levels. Overall, our study suggests that RASSF4 controls SOCE and ER-PM junctions through ARF6-dependent regulation of PM PI(4,5)P2 levels, pivotal for a variety of physiological processes.

SUBMITTER: Chen YJ 

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

REPOSITORIES: biostudies-literature

altmetric image

Publications

RASSF4 controls SOCE and ER-PM junctions through regulation of PI(4,5)P<sub>2</sub>.

Chen Yu-Ju YJ   Chang Chi-Lun CL   Lee Wan-Ru WR   Liou Jen J  

The Journal of cell biology 20170609 7


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 Ca<sup>2+</sup> entry (SOCE), a fundamental Ca<sup>2+</sup> signaling mechanism, by affecting the translocation of the endoplasmic reticulum (ER) Ca<sup>2+</sup> sensor stromal interaction molecule 1 (STIM1) to ER-plasma membrane (PM) junctions. It was further revealed that R  ...[more]

Similar Datasets

| S-EPMC5940310 | biostudies-literature
| S-EPMC7496663 | biostudies-literature
| S-EPMC3716012 | biostudies-literature
| S-EPMC9250379 | biostudies-literature
| S-EPMC7229175 | biostudies-literature
| S-EPMC5687020 | biostudies-literature
| S-EPMC4814223 | biostudies-literature
| S-EPMC3632088 | biostudies-other
| S-EPMC4843478 | biostudies-literature
| S-EPMC4828688 | biostudies-literature