Shank2 Binds to aPKC and Controls Tight Junction Formation with Rap1 Signaling during Establishment of Epithelial Cell Polarity
2020
Kazunori Sasaki | Noriko Kojitani | Hiroko Hirose | Yohei Yoshihama | Hidefumi Suzuki | Miho Shimada | Ayumi Takayanagi | Akio Yamashita | Masa-aki Nakaya | Hisashi Hirano | Hidehisa Takahashi | Shigeo Ohno
Summary: Epithelial cells establish apicobasal polarity by forming tight junctions (TJs) at the apical-lateral boundary, which play fundamental roles in physiological functions. An evolutionarily conserved atypical protein kinase C (aPKC)-partitioning defective (PAR) complex functions as a platform for TJ assembly during cell polarity establishment. However, how this complex converts the spatial cues into a subsequent active unit is unclear. Here, we identify an epithelial isoform of Shank2 as a mediator of the aPKC-PAR complex. Shank2 binds to and colocalizes with aPKC at apical junctional regions of polarized epithelial cells. Shank2 knockdown results in defects in TJ formation. Mechanistically, we find that the N-terminal SPN domain is required for the junctional localization of Shank2 and binds to the active form of Rap1 small GTPase, which is involved in TJ formation. Our findings suggest that a close physical and functional relationship between aPKC and Shank2-active Rap1 signaling serves as the platform for TJ assembly to regulate epithelial cell polarity. : Sasaki et al. demonstrate that epithelial Shank2 localizes at tight junctions (TJs) via its epithelia-specific N terminus and interacts with aPKC. Through small GTPase Rap1 signaling, the aPKC-Shank2 complex functions as a platform for TJ assembly during the establishment of the epithelial cell polarity. Keywords: cell polarity, tight junction, aPKC-PAR complex, Shank2, Rap1, SPN domain, ankyrin repeats
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