Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Graduate Program in Neuroscience, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Hum Genet. 2023 Aug;142(8):1263-1270. doi: 10.1007/s00439-023-02558-w. Epub 2023 Apr 22.
Exocytosis is the process by which secretory vesicles fuse with the plasma membrane to deliver materials to the cell surface or to release cargoes to the extracellular space. The exocyst-an evolutionarily conserved octameric protein complex-mediates spatiotemporal control of SNARE complex assembly for vesicle fusion and tethering the secretory vesicles to the plasma membrane. The exocyst participates in diverse cellular functions, including protein trafficking to the plasma membrane, membrane extension, cell polarity, neurite outgrowth, ciliogenesis, cytokinesis, cell migration, autophagy, host defense, and tumorigenesis. Exocyst subunits are essential for cell viability; and mutations or variants in several exocyst subunits have been implicated in human diseases, mostly neurodevelopmental disorders and ciliopathies. These conditions often share common features such as developmental delay, intellectual disability, and brain abnormalities. In this review, we summarize the mutations and variants in exocyst subunits that have been linked to disease and discuss the implications of exocyst dysfunction in other disorders.
胞吐作用是指分泌囊泡与质膜融合，将物质运送到细胞表面或向细胞外空间释放货物的过程。外泌体——一种进化上保守的八聚体蛋白复合物——介导 SNARE 复合物组装的时空控制，以实现囊泡融合和将分泌囊泡锚定在质膜上。外泌体参与多种细胞功能，包括蛋白质向质膜的运输、膜延伸、细胞极性、轴突生长、纤毛发生、胞质分裂、细胞迁移、自噬、宿主防御和肿瘤发生。外泌体亚基对于细胞活力是必需的；并且，几个外泌体亚基的突变或变体与人类疾病有关，主要是神经发育障碍和纤毛病。这些病症通常具有共同的特征，如发育迟缓、智力残疾和脑异常。在这篇综述中，我们总结了与疾病相关的外泌体亚基的突变和变体，并讨论了外泌体功能障碍在其他疾病中的意义。
