Calsenilin, a Presenilin Interactor, Regulates RhoA Signaling and Neurite Outgrowth
AbstractCalsenilin modulates A-type potassium channels, regulates presenilin-mediated γ-secretase activity, and represses prodynorphin and c-fos genes expression. RhoA is involved in various cellular functions including proliferation, differentiation, migration, transcription, and regulation of the actin cytoskeleton. Although recent studies demonstrate that calsenilin can directly interact with RhoA and that RhoA inactivation is essential for neuritogenesis, it is uncertain whether there is a link between calsenilin and RhoA-regulated neuritogenesis. Here, we investigated the role of calsenilin in RhoA-regulated neuritogenesis using in vitro and in vivo systems. We found that calsenilin induced RhoA inactivation, which accompanied RhoA phosphorylation and the reduced phosphorylation levels of LIM kinase (LIMK) and cofilin. Interestingly, PC12 cells overexpressing either full-length (FL) or the caspase 3-derived C-terminal fragment (CTF) of calsenilin significantly inactivated RhoA through its interaction with RhoA and p190 Rho GTPase-activating protein (p190RhoGAP). In addition, cells expressing FL and the CTF of calsenilin had increased neurite outgrowth compared to cells expressing the N-terminal fragment (NTF) of calsenilin or vector alone. Moreover, Tat-C3 and Y27632 treatment significantly increased the percentage of neurite-bearing cells, neurite length, and the number of neurites in cells. Finally, calsenilin deficiency in the brains of calsenilin-knockout mice significantly interfered with RhoA inactivation. These findings suggest that calsenilin contributes to neuritogenesis through RhoA inactivation. View Full-Text
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Kim, H.-J.; Lee, W.-H.; Kim, M.-J.; Shin, S.; Jang, B.; Park, J.-B.; Wasco, W.; Buxbaum, J.D.; Kim, Y.-S.; Choi, E.-K. Calsenilin, a Presenilin Interactor, Regulates RhoA Signaling and Neurite Outgrowth. Int. J. Mol. Sci. 2018, 19, 1196.
Kim H-J, Lee W-H, Kim M-J, Shin S, Jang B, Park J-B, Wasco W, Buxbaum JD, Kim Y-S, Choi E-K. Calsenilin, a Presenilin Interactor, Regulates RhoA Signaling and Neurite Outgrowth. International Journal of Molecular Sciences. 2018; 19(4):1196.Chicago/Turabian Style
Kim, Hee-Jun; Lee, Won-Haeng; Kim, Mo-Jong; Shin, Sunmee; Jang, Byungki; Park, Jae-Bong; Wasco, Wilma; Buxbaum, Joseph D.; Kim, Yong-Sun; Choi, Eun-Kyoung. 2018. "Calsenilin, a Presenilin Interactor, Regulates RhoA Signaling and Neurite Outgrowth." Int. J. Mol. Sci. 19, no. 4: 1196.
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