Kaminska Joanna
Institute of Biochemistry and Biophysics Polish Academy of Science, Warsaw, Poland.
Contact (Thousand Oaks). 2022 Jun 9;5:25152564221106024. doi: 10.1177/25152564221106024. eCollection 2022 Jan-Dec.
Mutations in the four human genes , encoding vacuolar protein sorting 13 (VPS13A-D) proteins, result in developmental or neurodegenerative diseases. Understanding the functioning of VPS13 proteins in physiology and pathology is a hot topic of research. Especially interesting is how VPS13 proteins are localized to specific membrane contact sites and function in lipid transport. Recently, the C-terminal Pleckstrin Homology (PH)-like domains of yeast Vps13 and human VPS13A were found to bind Arf1 GTPase and to phosphoinositol 4,5-bisphosphate. Here, hypotheses on the importance of the dual binding ability of the PH-like domain of VPS13A protein for cell physiology are presented. While yeast Vps13, together with Arf1 GTPase, is important for protein sorting in the Trans Golgi Network (TGN), the localization of VPS13A in TGN is speculated to restrict the binding of VPS13A to the plasma membrane.
编码液泡蛋白分选13（VPS13A-D）蛋白的四个人类基因发生突变会导致发育性疾病或神经退行性疾病。了解VPS13蛋白在生理学和病理学中的功能是一个研究热点。特别有趣的是VPS13蛋白如何定位于特定的膜接触位点并在脂质转运中发挥作用。最近，发现酵母Vps13和人类VPS13A的C末端类普列克底物蛋白同源（PH）结构域可结合Arf1 GTP酶和磷酸肌醇4,5-二磷酸。在此，提出了关于VPS13A蛋白的类PH结构域的双重结合能力对细胞生理学重要性的假说。虽然酵母Vps13与Arf1 GTP酶一起对反式高尔基体网络（TGN）中的蛋白质分选很重要，但推测VPS13A在TGN中的定位会限制VPS13A与质膜的结合。
