三聚体家族蛋白作为发育和疾病中细胞迁移和形态发生的调节剂——机制和细胞环境。
Trio family proteins as regulators of cell migration and morphogenesis in development and disease - mechanisms and cellular contexts.
机构信息
Department of Molecular Biochemistry and Biophysics, Yale School of Medicine, Yale University, New Haven, CT 06511 USA
出版信息
J Cell Sci. 2021 Feb 10;134(3):jcs248393. doi: 10.1242/jcs.248393.
Abstract
The well-studied members of the Trio family of proteins are Trio and kalirin in vertebrates, UNC-73 in and Trio in Trio proteins are key regulators of cell morphogenesis and migration, tissue organization, and secretion and protein trafficking in many biological contexts. Recent discoveries have linked Trio and kalirin to human disease, including neurological disorders and cancer. The genes for Trio family proteins encode a series of large multidomain proteins with up to three catalytic activities and multiple scaffolding and protein-protein interaction domains. As such, Trio family proteins engage a wide array of cell surface receptors, substrates and interaction partners to coordinate changes in cytoskeletal regulatory and protein trafficking pathways. We provide a comprehensive review of the specific mechanisms by which Trio family proteins carry out their functions in cells, highlight the biological and cellular contexts in which they occur, and relate how alterations in these functions contribute to human disease.
摘要
三肽基脯氨酰顺反异构酶（Trio）家族蛋白是研究较为透彻的蛋白家族，脊椎动物中包括 Trio 和 kalirin，秀丽隐杆线虫中则是 UNC-73，而在果蝇中则是 Trio。 Trio 蛋白是细胞形态发生和迁移、组织形成以及分泌和蛋白运输等许多生物学过程的关键调节因子。最近的发现将 Trio 和 kalirin 与人类疾病联系起来，包括神经紊乱和癌症。 Trio 家族蛋白的基因编码一系列具有多达三种催化活性和多个支架及蛋白-蛋白相互作用结构域的大型多结构域蛋白。因此， Trio 家族蛋白与广泛的细胞表面受体、底物和相互作用伙伴结合，以协调细胞骨架调节和蛋白运输途径的变化。我们全面回顾了 Trio 家族蛋白在细胞中发挥功能的具体机制，强调了它们发生的生物学和细胞环境，并阐述了这些功能的改变如何导致人类疾病。
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J Cell Sci. 2021 Feb 10;134(3):jcs248393. doi: 10.1242/jcs.248393.
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Opposite Modulation of RAC1 by Mutations in TRIO Is Associated with Distinct, Domain-Specific Neurodevelopmental Disorders.TRIO 基因突变导致 RAC1 的相反调节与不同的、特定于结构域的神经发育障碍相关。
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