Calsenilin regulates RhoA signaling and neurite outgrowth

• 발행기관: 한국노년학회
• 저자명: Hee-Jun Kim Won-Haeng Lee Mo-Jong Kim Piplu Bhuiyan Yong-Sun Kim Eun-Kyoung Choi
• 간행물 정보: 『한국노년학회 학술대회 논문집』2017년 한국노인과학학술대회, 261~261쪽, 전체 1쪽
• 주제분류: 사회과학 > 사회복지학
• 파일형태: PDF
• 발행일자: 2017.11.03

영문 초록

Calsenilin is a calcium sensor and multi-functional protein that modulates A-type potassium channels, regulates presenilin-mediated γ-secretase activity and represses the transcription of prodynorphin and c-fos genes. RhoA, a small GTPase protein, is involved in various cellular functions including proliferation, differentiation, migration, transcription, and regulation of actin cytoskeleton and cell morphology. Although recent studies demonstrated that calsenilin can be directly interacting with RhoA and that RhoA inactivation is essential for neuritogenesis, a possible link between calsenilin and RhoA-regulated neuritogenesis is still unclear. Here, we investigated the role of calsenilin on RhoA-regulated neuritogenesis using in vitro and in vivo systems. We found that calsenilin induced RhoA inactivation, which reduced RhoA phosphorylation and increased the phosphorylation levels of LIMK and cofilin during nerve growth factor (NGF)-induced neuronal differentiation in PC12 cells. Interestingly, PC12 cells overexpressing full-length and caspase 3-derived C-terminal fragment (CTF) of calsenilin significantly increased RhoA inactivation through the interaction with RhoA and enhanced the interaction between RhoA and p190RhoGAP. In addition, cells expressing full-length and calsenilin-CTF increased neurite outgrowth, number of branches, and neurite length compared to cells expressing either N-terminal fragment (NTF) of calsenilin or vector alone. In addition, we found the changes in the expression of some of microRNAs which are involved in neuronal differentiation. Currently, we identify differential expression of microRNAs that are involved in neuronal differentiation. Finally, we observed that the absence of calsenilin significantly reduced RhoA inactivation in the brains of calsenilin knockout mice. These findings suggest that calsenilin contributes to neuritogenesis through the RhoA inactivation and its signaling.

키워드

Calsenilin RhoA p190RhoGAP Nurite outgrowth