Speaker Professor Neil McDonald, Group Leader and Head of the Signalling and Structural Biology Laboratory, The Francis Crick Institute

Title Kinase-driven control mechanisms for cell polarity

Host Sasi Conte

 

Abstract The PAR-titioning-defective or PAR proteins are key components of an essential cell polarity network conserved throughout the animal kingdom. This network underlies polarization in a wide variety of cell types from neurons, epithelial cells and migrating cells, impacting on membrane identity and asymmetric cell division. The main components of the network include the serine/threonine kinases, aPKC and PAR-1, the 14-3-3 protein PAR-5, the PDZ-containing scaffold proteins PAR-3/Bazooka and PAR-6, the small Rho-family GTPase CDC-42, and Lethal Giant Larva (LGL), a multi-site substrate of aPKC. These proteins are functionally organised into two opposing groups that mutually antagonise each other within the polarity network. The precise mechanism of mutual antagonism is not known. In my presentation I will discuss our recent data explaining how aPKC selectively targets the crucial polarity substrates LGL and the PAR-1 kinase, revealing the origin of their mutual antagonism in polarised cells. By combining cryo-EM structures and cell-based assays with in vivo models of polarity we develop an integrated model for both single-site and multi-site substrate phosphorylation and determine the consequences of substrate phosphorylation.