A casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning.

2.50
Hdl Handle:
http://hdl.handle.net/10541/68736
Title:
A casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning.
Authors:
Panbianco, Costanza; Weinkove, David; Zanin, Esther; Jones, David R; Divecha, Nullin; Gotta, Monica; Ahringer, Julie
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.
Affiliation:
The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB21QN, UK.
Citation:
A casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning. 2008, 15 (2):198-208 Dev. Cell
Journal:
Developmental Cell
Issue Date:
Aug-2008
URI:
http://hdl.handle.net/10541/68736
DOI:
10.1016/j.devcel.2008.06.002
PubMed ID:
18694560
Type:
Article
Language:
en
ISSN:
1534-5807
Appears in Collections:
Inositide Laboratory; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPanbianco, Costanza-
dc.contributor.authorWeinkove, David-
dc.contributor.authorZanin, Esther-
dc.contributor.authorJones, David R-
dc.contributor.authorDivecha, Nullin-
dc.contributor.authorGotta, Monica-
dc.contributor.authorAhringer, Julie-
dc.date.accessioned2009-05-21T16:32:09Z-
dc.date.available2009-05-21T16:32:09Z-
dc.date.issued2008-08-
dc.identifier.citationA casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning. 2008, 15 (2):198-208 Dev. Cellen
dc.identifier.issn1534-5807-
dc.identifier.pmid18694560-
dc.identifier.doi10.1016/j.devcel.2008.06.002-
dc.identifier.urihttp://hdl.handle.net/10541/68736-
dc.description.abstractSpindle 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.en
dc.language.isoenen
dc.subjectCell Divisionen
dc.subject.meshAnimals-
dc.subject.meshCaenorhabditis elegans-
dc.subject.meshCaenorhabditis elegans Proteins-
dc.subject.meshCasein Kinase I-
dc.subject.meshCell Nucleus-
dc.subject.meshEmbryo, Nonmammalian-
dc.subject.meshMitotic Spindle Apparatus-
dc.subject.meshModels, Biological-
dc.subject.meshPhosphatidylinositol 4,5-Diphosphate-
dc.subject.meshPhosphotransferases (Alcohol Group Acceptor)-
dc.subject.meshProtein Transport-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshRNA Interference-
dc.titleA casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning.en
dc.typeArticleen
dc.contributor.departmentThe Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB21QN, UK.en
dc.identifier.journalDevelopmental Cellen

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