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Sci. Signal., 1 July 2008
Vol. 1, Issue 26, p. ec241
[DOI: 10.1126/scisignal.126ec241]

EDITORS' CHOICE

Cell Polarization Polarity Proteins Get Excluded

Annalisa M. VanHook

Science Signaling, AAAS, Washington, DC 20005, USA

Early embryonic morphogenetic events such as gastrulation and cell fate specification often rely on radial polarization of the embryo. In the nematode Caenorhabditis elegans, several polarity proteins, including the PDZ-containing PAR-6, are localized to the uncontacted outer surface of each of the early embryonic somatic (EES) cells from the four-cell stage through gastrulation. The "outer surface" here is defined as that part of an EES cell’s membrane that does not contact other EES cells and corresponds to the outside surface of the embryo. These polarity proteins act as landmarks that enable the cells to undergo the asymmetric shape changes that direct gastrulating cells inward. Anderson et al. identified PAR-6-at-contacts (pac-1) in a screen for mutations that affect the localization of PAR-6 in EES cells. PAC-1 was required for the localization of PAR-6, PAR-3, and atypical protein kinase C (PKC-3) to the outer cortex of the early embryo, as all three proteins were distributed uniformly over the EES cell surfaces in pac-1 mutants. The accumulation of activated (phosphorylated) myosin regulatory light chain (p-rMLC) on the outer surfaces of EES cells decreased in pac-1 mutants as compared with wild type. This cortical myosin contractile network drives the cell ingressions that define gastrulation; thus, gastrulation slowed in pac-1 mutants. A transgenically expressed green fluorescent protein (GFP)-tagged version of PAC-1 rescued the pac-1 mutant phenotype and localized to the inner surfaces of EES cells, where cells contacted one another. PAC-1 contained a pleckstrin homology (PH) domain and a Rho GTPase-activating protein (RhoGAP) domain. Genetic experiments demonstrated that the RhoGAP domain of PAC-1 was required to both establish and maintain the asymmetric distribution of PAR-6 in EES cells. The Rho GTPase CDC42, which is required for PAR-6 localization, was identified as the most likely PAC-1 substrate on the basis of genetic and expression data. The authors propose a model in which PAC-1 inhibits CDC42 where cells contact one another, thereby restricting active CDC42 to the cell’s outer cortex, where it mediates the assembly of the polarity complex composed of PAR-6, PAR-3, and PKC-3.

D. C. Anderson, J. S. Gill, R. M. Cinalli, J. Nance, Polarization of the C. elegans embryo by RhoGAP-mediated exclusion of PAR-6 from cell contacts. Science 320, 1771-1774 (2008). [Abstract] [Full Text]

Citation: A. M. VanHook, Polarity Proteins Get Excluded. Sci. Signal. 1, ec241 (2008).



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