Epithelial cell polarity requires the formation of a tripartite complex among atypical protein kinase C (aPKC), PAR-3 and PAR-6. At the same time, GTP exchange factor (GEF)-mediated signalling from the Gαi G-protein subunits has been implicated in establishing apico-basal polarity in epithelia. To elucidate the links between PAR–aPKC and G-protein signalling, Shigeo Ohno and colleagues (p. 2244) focused on Girdin, a non-receptor GEF for Gαi, and discovered a novel signalling pathway that is vital for establishing polarity. They showed that the PAR-3–aPKC complex functionally interacts with the AP-2α transcription factor to upregulate Girdin expression. Mechanistically, Girdin was found to interact with both PAR-3 and Gαi3. Knockdown (KD) of Girdin caused a disruption in F-actin organisation, a delay in the formation of tight junctions and an aberrant number of vacuolar apical compartments, indicating a problem with the formation of apical domains. In addition, overexpression of Girdin was able to partially rescue the polarisation defects of PAR-3 KD cells. The authors also demonstrated that Girdin can rescue the effects of PAR-3 KD in 3D-cultured cysts and that a disruption of the binding of Girdin to Gαi3 causes severe cyst deformations. Taken together, these results reveal a novel, dual role for PAR-3 in establishing epithelial cell polarity through the regulation of Girdin transcription and the PAR-3–Girdin–Gαi3 signalling axis.
PAR-3 regulates polarity through Girdin
PAR-3 regulates polarity through Girdin. J Cell Sci 1 July 2015; 128 (13): e1301. doi:
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