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.

胞吐作用是分泌囊泡与质膜融合以将物质递送至细胞表面或将货物释放至细胞外空间的过程。外囊——一种进化上保守的八聚蛋白复合物——介导 SNARE 复合物组装的时空控制，以实现囊泡融合并将分泌囊泡束缚到质膜上。外囊参与多种细胞功能，包括蛋白质运输到质膜、膜延伸、细胞极性、神经突生长、纤毛发生、胞质分裂、细胞迁移、自噬、宿主防御和肿瘤发生。胞外囊亚基对于细胞活力至关重要；一些外囊亚基的突变或变异与人类疾病有关，主要是神经发育障碍和纤毛病。这些疾病通常具有共同特征，例如发育迟缓、智力障碍和大脑异常。在这篇综述中，我们总结了与疾病相关的外囊亚基的突变和变异，并讨论了外囊功能障碍在其他疾病中的影响。