Epithelial apico-basal polarity specification and remodeling relies on a set of conserved factors including Baz, Par6 and aPKC, together with Crb, Sdt and PATJ. Despite significant attention directed at studying these genes function during epithelial cell polarity, a surprising few studies have been dedicated to PATJ. Part of the issue is the fact that no single mutant in the patj locus is available. To date, we do not know how PATJ integrates with Crb, Sdt, Par6-aPKC and Baz during epithelial polarity specification and remodeling.
In order to examine in detail the relationship between these factors, I am studying patj function during epithelial cell polarity remodeling. I am mostly making use of the developing photoreceptor, combined to genetics and biochemistry in S2R+ cells.
Epithelial cells are characterized by distinct apical and basal membrane domains that are separated by sites of cell-cell contact, including the zonula adherens (za). During development these discrete domains must be specified, maintained and remodelled. A number of conserved polarity determinants have been identified, and these promote epithelial morphogenesis within genetically defined networks. However, our understanding of the interplay between these factors is incomplete.
Several key determinants central to my work are Bazooka (Baz), the Par6-DaPKC module together with Crumbs (Crb), Stardust (Sdt) and PATJ. I have shown that during apico-basal remodeling and Crb is responsible for excluding Baz from the sub-apical domain where its canonical binding partners DaPKC and Par6 reside. This molecular sorting mechanism also requires the phosphorylation of Baz by DaPKC. Consequently, Baz defines the location of the cell the za, where it recruits adherens junction material. While binding of the Rho-GTPase Cdc42 to Par6 is not required for Baz phosphorylation by DaPKC, it is required for optimum recruitment of Crb at the sub-apical membrane. I now in the process of further characterizing the interplay between cdc42, Crb, Baz, Par6-DaPKC and the several component of the polarity gene network such as E-Cadherin, Lgl and Par1.
NEURONAL POLARITY & MORPHOGENESIS