Open AccessPlasma membrane processes differentially regulated by type I phosphatidylinositol phosphate 5-kinases and RASSF4
Author(s) -
Lizbeth de la Cruz,
Alexis TraynorKaplan,
Oscar Vivas,
Bertil Hille,
Jill B. Jensen
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.233254
Subject(s) - phosphatidylinositol , microbiology and biotechnology , biology , phosphatidylinositol 4,5 bisphosphate , kinase , stim1 , membrane , biochemistry , endoplasmic reticulum
Phosphoinositide lipids regulate many cellular processes. They are synthesized by lipid kinases. Type I phosphatidylinositol phosphate 5-kinases (PIP5KIs) generate phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2). Several phosphoinositide-sensitive readouts revealed nonequivalence of overexpressing PIP5KIβ or PIP5KIγ or RASSF4, believed to activate PIP5KIs. Mass spectrometry showed each protein increased total cellular PtdInsP2 and PtdInsP3 at the expense of PtdInsP without changing lipid acyl chains. KCNQ2/3 channels and PH domains confirmed an increase of plasma membrane PtdIns(4,5)P2 with PIP5KIβ or PIP5KIγ overexpression, but RASSF4 required coexpression with PIP5KIγ to increase plasma membrane PtdIns(4,5)P2. Effects on the several steps of store-operated calcium entry (SOCE) were not explained by plasma membrane phosphoinositide increases alone. PIP5KIβ and RASSF4 increased STIM1 proximity to the plasma membrane and accelerated mobilization and faster onset of SOCE. But PIP5KIγ reduced STIM1 recruitment yet did not change induced Ca2+ entry. These differences imply actions through different segregated pools of phosphoinositides and specific protein-protein interactions and targeting.