A Casein Kinase 1 and PAR Proteins Regulate Asymmetry of a PIP2 Synthesis Enzyme for Asymmetric Spindle Positioning

Costanza Panbianco,David Weinkove,Esther Zanin,David Jones,Nullin Divecha,Monica Gotta,Julie Ahringer

doi:10.1016/j.devcel.2008.06.002

Abstract

SummarySpindle 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 Gα regulators GPR-1/2. Here, we establish that the casein kinase 1 gamma CSNK-1 and a PIP2 synthesis enzyme (PPK-1) transduce PAR polarity to asymmetric Gα 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 PIP2. We propose that asymmetric generation of PIP2 by PPK-1 directs the posterior enrichment of GPR-1/2 and LIN-5, leading to posterior spindle displacement.

Highlights

Asymmetric cell divisions are important for the fate and diversity of many animal cells
We establish that the casein kinase 1 gamma CSNK-1 and a PIP2 synthesis enzyme (PPK-1) transduce PAR polarity to asymmetric Ga regulation
Knockdown of ppk-1 leads to low GPR-1/2 levels and decreased spindle forces

Summary

Introduction

Asymmetric cell divisions are important for the fate and diversity of many animal cells (reviewed in Betschinger and Knoblich, 2004). A wealth of studies from many systems has shown that the molecules involved in cell polarization and spindle positioning are similar in different animal cells, suggesting the existence of a universal mechanism that has been conserved throughout evolution. PAR polarity proteins are used for polarization, and they control spindle position through regulation of heterotrimeric G protein signaling (reviewed in McCarthy and Goldstein, 2006). The C. elegans embryo is an important model for studying asymmetric cell division (reviewed in Schneider and Bowerman, 2003). In the one-celled C. elegans embryo, a complex of PAR-3 and PAR-6, two PDZ-domain-containing proteins, together with atypical protein kinase C PKC-3 are found at the anterior. The precise mechanism by which the PAR proteins coordinate polarity with spindle positioning remains to be elucidated; G protein signaling has been identified as the major spindle force transducer

Results

Discussion

Conclusion