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Review
. 2023 Aug;142(8):1263-1270.
doi: 10.1007/s00439-023-02558-w. Epub 2023 Apr 22.

The exocyst complex in neurological disorders

Dilara O Halim  1   2 , Mary Munson  3 , Fen-Biao Gao  4   5
Affiliations
Review

The exocyst complex in neurological disorders

Dilara O Halim et al. Hum Genet. 2023 Aug.

Abstract

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.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Diverse functions of the exocyst. The exocyst, an octameric complex consisting of EXOC1-8 subunits, functions as an effector of RALA and RALB GTPase signaling mediated by EXOC2 and EXOC8 binding. The interaction with RALA is also important for the assembly of the complex. The exocyst has diverse roles, including protein trafficking, vesicle tethering to the plasma membrane for secretion, cytokinesis, neurite outgrowth, and ciliogenesis. Through its interaction with RALA, the exocyst also participates in cell migration and tumor invasion. The interaction between EXOC8 and RALB regulates autophagy initiation, and EXOC2 and RALB together serve as a scaffold to recruit and activate TBK1 for host defense and survival of cancer cells. EXOC1: yellow, EXOC2: light green, EXOC3: magenta, EXOC4: dark green, EXOC5: cyan, EXOC6: red, EXOC7: dark blue, EXOC8: pink. Partially created with BioRender.com
See this image and copyright information in PMC

References

    1. Aoki Y, Niihori T, Inoue SI, Matsubara Y. Recent advances in RASopathies. J Hum Genet. 2016;61:33–39. doi: 10.1038/jhg.2015.114. - DOI - PubMed
    1. Badano JL, Mitsuma N, Beales PL, Katsanis N. The ciliopathies: An emerging class of human genetic disorders. Annu Rev Genomics Hum Genet. 2006;7:125–148. doi: 10.1146/annurev.genom.7.080505.115610. - DOI - PubMed
    1. Van Bergen NJ, Ahmed SM, Collins F, Cowley M, Vetro A, Dale RC, Hock DH, de Caestecker C, Minal M, Massey S, Gladys H, Pisano T, Glover S, Gusman J, Stroud DA, Dinger M, Guerrini R, MacAra IG, Christodoulou J. Mutations in the exocyst component EXOC2 cause severe defects in human brain development. J Exp Med. 2020;217:e20192040. doi: 10.1084/JEM.20192040. - DOI - PMC - PubMed
    1. Bodemann BO, White MA. Ral GTPases and cancer: Linchpin support of the tumorigenic platform. Nat Rev Cancer. 2008;8:133–140. doi: 10.1038/nrc2296. - DOI - PubMed
    1. Borsani G, Piovani G, Zoppi N, Bertini V, Bini R, Notarangelo L, Barlati S. Cytogenetic and molecular characterization of a de-novo t(2p;7p) translocation involving TNS3 and EXOC6B genes in a boy with a complex syndromic phenotype. Eur J Med Genet. 2008;51:292–302. doi: 10.1016/j.ejmg.2008.02.006. - DOI - PubMed

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