Neural‐Specific Expression and Membrane Localization of <scp>FAM163B</scp> Regulates <scp>SAP97</scp> Expression

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.