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Projekt
Coordinate regulation of apical-basal cell polarity and cell-cell adhesion during epithelial development
Antragsteller
Professor Dr. Andreas Wodarz
Fachliche Zuordnung
Entwicklungsbiologie
Förderung
Förderung von 2011 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 200509276
The formation of the zonula adherens (ZA), an adhesion belt encircling the apical region of the lateral plasma membrane in epithelial cells, is tightly coordinated with the establishment of apical-basal cell polarity. In Drosophila, mutations in genes required for the control of cell polarity, e. g. crumbs (crb), stardust (sdt), bazooka (baz) and aPKC, also affect the formation of the ZA. The formation of spot adherens junctions (AJs), which coalesce to build the contiguous belt of the ZA, requires the function of the homophilic cell-cell adhesion protein DE-cadherin and its binding partners, α- and β-catenin. Spot AJs still form in mutants for the polarity regulators, but their coordinate movement to the apical region of the lateral membrane and their fusion during ZA formation is abolished. Furthermore, the ZA cannot be maintained in epithelia undergoing morphogenetic movements when the function of the polarity regulators is impaired. So far, only limited information is available to understand the crosstalk between the polarity regulators and the proteins of the cadherin-catenin complex, which mediate the adhesion between epithelial cells. In a yeast two-hybrid-screen for interaction partners of Baz, a central regulator of apical-basal polarity in epithelia, we isolated the LIM domain protein encoded by the annotated gene CG31534. CG31534 binds to Baz in vivo and colocalizes precisely with Baz and DE-cadherin at the ZA of ectodermal epi-thelia. CG31534 also binds to and gets phosphorylated by the tyrosine kinase Src42A, which has been implicated in the phosphorylation and regulation of β-catenin. In this project, we will analyze the function of CG31534 and its vertebrate homolog LMO7 with respect to regulation of Src42A activity during ZA formation and junctional remodeling in development.
DFG-Verfahren
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