iASPP regulates neurite development by interacting with Spectrin proteins

Junhao Wang; Chunhong Jia; Qiong Gao; Jiwen Zhang; Xi Gu

doi:10.3389/fnmol.2023.1154770

iASPP regulates neurite development by interacting with Spectrin proteins

Front Mol Neurosci. 2023 May 22:16:1154770. doi: 10.3389/fnmol.2023.1154770. eCollection 2023.

Authors

Junhao Wang¹, Chunhong Jia², Qiong Gao¹, Jiwen Zhang¹, Xi Gu¹

Affiliations

¹ Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
² Department of Neonatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Abstract

Introduction: Since its discovery in 1999, a substantial body of research has shown that iASPP is highly expressed in various kinds of tumors, interacts with p53, and promotes cancer cell survival by antagonizing the apoptotic activity of p53. However, its role in neurodevelopment is still unknown.

Methods: We studied the role of iASPP in neuronal differentiation through different neuronal differentiation cellular models, combined with immunohistochemistry, RNA interference and gene overexpression, and studied the molecular mechanism involved in the regulation of neuronal development by iASPP through coimmunoprecipitation coupled with mass spectrometry (CoIP-MS) and coimmunoprecipitation (CoIP).

Results: In this study, we found that the expression of iASPP gradually decreased during neuronal development. iASPP silencing promotes neuronal differentiation, while its overexpression inhibited neurite differentiation in a variety of neuronal differentiation cellular models. iASPP associated with the cytoskeleton-related protein Sptan1 and dephosphorylated the serine residues in the last spectrin repeat domain of Sptan1 by recruiting PP1. The non-phosphorylated and phosphomimetic mutant form of Sptbn1 inhibited and promoted neuronal cell development respectively.

Conclusion: Overall, we demonstrate that iASPP suppressed neurite development by inhibiting phosphorylation of Sptbn1.

Keywords: Sptan1; Sptbn1; iASPP; neurite development; phosphorylation modification.