title: A casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning.
abstract: Spindle positioning is an essential feature of asymmetric cell division. The conserved PAR proteins together with heterotrimeric G proteins control spindle positioning in animal cells, but how these are linked is not known. In C. elegans, PAR protein activity leads to asymmetric spindle placement through cortical asymmetry of Galpha regulators GPR-1/2. Here, we establish that the casein kinase 1 gamma CSNK-1 and a PIP(2) synthesis enzyme (PPK-1) transduce PAR polarity to asymmetric Galpha regulation. PPK-1 is posteriorly enriched in the one-celled embryo through PAR and CSNK-1 activities. Loss of CSNK-1 causes uniformly high PPK-1 levels, high symmetric cortical levels of GPR-1/2 and LIN-5, and increased spindle pulling forces. In contrast, knockdown of ppk-1 leads to low GPR-1/2 levels and decreased spindle forces. Furthermore, loss of CSNK-1 leads to increased levels of PIP(2). We propose that asymmetric generation of PIP(2) by PPK-1 directs the posterior enrichment of GPR-1/2 and LIN-5, leading to posterior spindle displacement.
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB21QN, UK.
authors.forename: Costanza
authors.initials: C
authors.lastname: Panbianco
authors.forename: David
authors.initials: D
authors.lastname: Weinkove
authors.forename: Esther
authors.initials: E
authors.lastname: Zanin
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.forename: Nullin
authors.initials: N
authors.lastname: Divecha
authors.forename: Monica
authors.initials: M
authors.lastname: Gotta
authors.forename: Julie
authors.initials: J
authors.lastname: Ahringer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D047389:Casein Kinase I / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D008954:Models, Biological; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D008941:Spindle Apparatus / Q000201:enzymology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; C409406:PAR-1 protein, C elegans; D017853:Phosphotransferases (Alcohol Group Acceptor); C531146:Ppk-1 protein, C elegans; D047389:Casein Kinase I; D017346:Protein Serine-Threonine Kinases