Coupling of cell polarity & Rho GTPase signaling

Polarity proteins have emerged as key integrators of asymmetry in a range of cellular systems. Cell polarization requires the dynamic coupling of polarity signals with cytoskeletal regulation. Our work contributed to growing evidence of intimate cross-talk between polarity proteins and different Rho GTPases that drives cellular asymmetry e.g. during junction formation, cell migration and oriented cell division (Dias Gomes, Letzian et al., Nat Comm 2019). During mitosis of monolayered epithelial cells, the Par3-binding partner JAM-A triggers a transient activation of Cdc42 and PI(3) kinase, generates a gradient of PtdIns(3,4,5)P3 at the cortex and regulates the formation of the cortical actin cytoskeleton required for planar spindle orientation and sheet expansion (Tuncay et al., Nat Commun 2015). Furthermore, Par3, the small GTPase Rac and its activator Tiam1 promote front-rear polarization and motility of migrating keratinocytes, astrocytes and fibroblasts, respectively, indicating that next to their role in epithelial junction biogenesis a Par3-Tiam1/Rac signaling axis can support the efficient regeneration of different mammalian tissues (Iden & Collard NRMCB 2008; Ellenbroek et al., Small GTPases 2012).

Finally, in collaborative work using both murine and Drosophila animal models we could recently delineate functions of Par3A and Par3B in the kidney. Simultaneous inactivation of both Par3 proteins in mouse podocytes causes a severe kidney disease phenotype, likely due to RhoA-dependent regulation of podocyte architecture independently of aPKC (Köhler et al., bioRxiv 2020).