title: The dual PH domain protein Opy1 functions as a sensor and modulator of PtdIns(4,5)P₂ synthesis.
abstract: Phosphatidylinositol-4,5-bisphosphate, PtdIns(4,5)P(2), is an essential signalling lipid that regulates key processes such as endocytosis, exocytosis, actin cytoskeletal organization and calcium signalling. Maintaining proper levels of PtdIns(4,5)P(2) at the plasma membrane (PM) is crucial for cell survival and growth. We show that the conserved PtdIns(4)P 5-kinase, Mss4, forms dynamic, oligomeric structures at the PM that we term PIK patches. The dynamic assembly and disassembly of Mss4 PIK patches may provide a mechanism to precisely modulate Mss4 kinase activity, as needed, for localized regulation of PtdIns(4,5)P(2) synthesis. Furthermore, we identify a tandem PH domain-containing protein, Opy1, as a novel Mss4-interacting protein that partially colocalizes with PIK patches. Based upon genetic, cell biological, and biochemical data, we propose that Opy1 functions as a coincidence detector of the Mss4 PtdIns(4)P 5-kinase and PtdIns(4,5)P(2) and serves as a negative regulator of PtdIns(4,5)P(2) synthesis at the PM. Our results also suggest that additional conserved tandem PH domain-containing proteins may play important roles in regulating phosphoinositide signalling.
authors.affiliation: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
authors.forename: Yading
authors.initials: Y
authors.lastname: Ling
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stefan
authors.forename: Jason A
authors.initials: JA
authors.lastname: Macgurn
authors.forename: Anjon
authors.initials: A
authors.lastname: Audhya
authors.forename: Scott D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C575030:Opy1 protein, S cerevisiae; D019269:Phosphatidylinositol 4,5-Diphosphate; D029701:Saccharomyces cerevisiae Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; C489795:MSS4 protein, S cerevisiae