Abstract:
Sorting nexins (SNXs) are a family of membrane-binding proteins known to play a critical role in regulating endocytic pathway sorting and endosomal membrane trafficking. Among them, SNX1 and SNX2 are members of the SNX-BAR subfamily and possess a membrane-curvature domain and a phosphoinositide-binding domain, which enables their stabilization at the phosphatidylinositol-3-phosphate (PI3P)-positive surface of endosomes. While their binding to PI3P-positive platforms facilitates interaction with endosomal partners and stabilization at the endosomal membrane, their SNX-BAR region is pivotal for generating membrane tubulation from endosomal compartments. In this context, their primary identified biological roles-and their partnership-are tightly associated with the retromer and endosomal SNX-BAR sorting complex for promoting exit 1 complex trafficking, facilitating the transport of cargoes from early endosomes to the secretory pathway. However, recent literature indicates that these proteins also possess biological functions in other aspects of endosomal features and sorting processes. Notably, SNX2 has been found to regulate endosome-endoplasmic reticulum (ER) contact sites through its interaction with VAP proteins at the ER membrane. Furthermore, data from our laboratory show that SNX1 and SNX2 are involved in the tubulation of early endosomes toward ER sites associated with autophagy initiation during starvation. These findings shed light on a novel role of SNXs in inter-organelle tethering and communication. In this concise review, we will explore the non-retromer functions of SNX1 and SNX2, specifically focusing on their involvement in endosomal membrane dynamics during stress sensing and autophagy-associated processes.
摘要:
分选nexin(SNX)是膜结合蛋白家族,已知在调节内吞途径分选和内体膜运输中起关键作用。其中,SNX1和SNX2是SNX-BAR亚家族的成员,具有膜曲率域和磷酸肌醇结合域,这使得它们能够在内体的磷脂酰肌醇-3-磷酸(PI3P)-阳性表面上稳定。虽然它们与PI3P阳性平台的结合促进了与内体伴侣的相互作用和内体膜的稳定,它们的SNX-BAR区对于从内体区室产生膜管至关重要。在这种情况下,它们主要确定的生物学作用-及其伙伴关系-与促进出口1复合物贩运的逆转录和内体SNX-BAR分选复合物密切相关,促进货物从早期内体运输到分泌途径。然而,最近的文献表明,这些蛋白质在内体特征和分选过程的其他方面也具有生物学功能。值得注意的是,已发现SNX2通过与ER膜上的VAP蛋白相互作用来调节内体-内质网(ER)接触位点。此外,我们实验室的数据显示,SNX1和SNX2参与早期内体向与饥饿期间自噬启动相关的ER位点的插管.这些发现揭示了SNX在细胞器间束缚和交流中的新作用。在这篇简明的评论中,我们将探讨SNX1和SNX2的非逆转录功能,特别是它们在应激感知和自噬相关过程中参与内体膜动力学。