Doerflinger, H.; Palandri, A.; Jackaman, N.; Chen, Y.; Zhu, X.; St Johnston, D.

Apical-basal polarity in epithelial cells is controlled by a conserved set of polarity factors that define the apical, junctional and basolateral domains of the cell, but how these factors adapt to or control changes in domain sizes during cell shape changes remains unclear. Atypical protein kinase C (aPKC) is the main effector of apical identity, phosphorylating the lateral factors, Bazooka/Par-3, Lgl, Par-1 and Yurt to exclude them from the apical domain. Using analogue-sensitive aPKC in Drosophila follicle cells , we found that aPKC s ubstrates differ over 100-fold in their sensitivity to inhibition, revealing a hierarchy of substrates, that is conserved in mammals in which high-affinity substrates out-compete low-affinity substrates when aPKC activity is limiting. Mild aPKC inhibition prevents the phosphorylation of its lowest affinity substrate, Yurt. Yurt then accumulates apically by binding to Crumbs, where it activates apical constriction through Shroom, Cysts/Dp114RhoGEF, Rho kinase and Myosin. Yurt localises apically in cells that are stretched, either by morphogenesis or artificially, indicating that stretching reduces aPKC activity to trigger an antagonistic contraction. By contrast, yurt-cells fail to resist stretching. Thus, the aPKC/Yurt pathway functions as a homeostatic stretch response, in which apical and lateral epithelial polarity factors collaborate to mechanically regulate apical domain size.