Neural-Specific Expression and Membrane Localization of FAM163B Regulates SAP97 Expression

IF 4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Neurochemistry Pub Date : 2025-09-25 DOI:10.1111/jnc.70244

Xiaoyu Zhang, Shanshan Sun, Wei Zhao, Yan Jiang, Yuting Weng, Ilgiz Gareev, Xuemin Ge, Xinrong Li, Jiaqi Wang, Qiongqiong Hu, Dechun Cheng, Lili Mu, Jinghua Wang

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Abstract

The cell membrane plays a significant role in the development and functional maintenance of neurons. However, the functions of many neuronal membrane proteins remain unclear, posing a challenge to the treatment of brain diseases. Family with sequence similarity 163 member B (FAM163B) is a single-transmembrane protein, and FAM163B is a neuroregulatory gene with unknown functions. In this study, we aimed to elucidate the function of FAM163B in neurons of the mouse brain. FAM163B was exclusively expressed in the mouse brain among various tissues analyzed. Immunoblotting, real-time PCR, and cellular immunofluorescence confirmed high expression of FAM163B in mouse neurons, which were mainly located in the cell membrane. Overexpression of FAM163B in SH-SY5Y cells and primary mouse cortical neurons resulted in downregulated expression of SAP97, and knockdown of FAM163B increased the expression level of SAP97. SAP97 is an important transporter that plays a part in synaptic function and neuroplasticity. Besides, an interaction was found between FAM163B and VAPA. VAPA is involved in the intracellular vesicle transport and membrane fusion processes. By staining with FM4-64FX, overexpression of FAM163B weakened the endocytosis ability of neurons, while knockdown enhanced it. The study provides for an understanding of the roles of FAM163B in neurons.

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FAM163B的神经特异性表达和膜定位调控SAP97的表达

细胞膜在神经元的发育和功能维持中起着重要作用。然而，许多神经元膜蛋白的功能仍不清楚，这给脑疾病的治疗带来了挑战。家族序列相似163成员B （FAM163B）是一种单跨膜蛋白，FAM163B是一种功能未知的神经调节基因。在本研究中，我们旨在阐明FAM163B在小鼠大脑神经元中的功能。在所分析的各组织中，FAM163B仅在小鼠脑中表达。免疫印迹、实时PCR和细胞免疫荧光证实FAM163B在小鼠神经元中高表达，主要位于细胞膜。SH-SY5Y细胞和原代小鼠皮质神经元中FAM163B的过表达导致SAP97表达下调，而FAM163B的下调使SAP97表达水平升高。SAP97是一种重要的转运体，在突触功能和神经可塑性中起作用。FAM163B与VAPA之间存在相互作用。VAPA参与细胞内囊泡运输和膜融合过程。FM4-64FX染色显示，过表达FAM163B会减弱神经元的内吞能力，而敲低FAM163B会增强神经元的内吞能力。本研究为了解FAM163B在神经元中的作用提供了依据。

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来源期刊

Journal of Neurochemistry 医学-神经科学

CiteScore

9.30

自引率

2.10%

发文量

181

审稿时长

2.2 months

期刊介绍： Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.