一个基因，多种表型：KIF5A在神经退行性疾病和神经发育疾病中的作用

One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.

作者信息

Cozzi Marta, Tedesco Barbara, Ferrari Veronica, Chierichetti Marta, Pramaggiore Paola, Cornaggia Laura, Magdalena Rocio, Brodnanova Maria, Mohamed Ali, Milioto Carmelo, Piccolella Margherita, Galbiati Mariarita, Rusmini Paola, Crippa Valeria, Gellera Cinzia, Magri Stefania, Taroni Franco, Cristofani Riccardo, Poletti Angelo

机构信息

Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti" (DiSFeB), University of Milan, Milan, 20133, Italy.

Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

出版信息

Cell Commun Signal. 2025 Jun 16;23(1):287. doi: 10.1186/s12964-025-02277-x.

DOI:10.1186/s12964-025-02277-x

PMID:40524150

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12172243/

Abstract

UNLABELLED

Kinesin family member 5 A (KIF5A) is a neuron-specific molecular motor involved in anterograde transport. KIF5A mediates a wide range of trafficking processes that are only partially shared with the other members of the KIF5 family. Since 2002, several disease-causing mutations have been found in the gene and a link between the specific domain in the encoded protein affected by mutations and the associated phenotype has become evident. Point mutations targeting KIF5A motor and stalk domains, that are expected to impair KIF5A motility, mainly associate with spastic paraplegia type 10 (SPG10) and axonal Charcot-Marie-Tooth (CMT) disease. Oppositely, translational frameshifts causing the elongation of KIF5A tail enhance KIF5A migration towards cell periphery, induce kinesin aggregation, and are linked to amyotrophic lateral sclerosis (ALS) or neonatal intractable myoclonus (NEIMY). This review correlates KIF5A structure and roles in neuronal trafficking with its involvement in the above-mentioned neurodegenerative and neurodevelopmental conditions.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12964-025-02277-x.

摘要

未标注

驱动蛋白家族成员5A（KIF5A）是一种参与顺向运输的神经元特异性分子马达。KIF5A介导多种运输过程，这些过程仅部分与KIF5家族的其他成员共享。自2002年以来，已在该基因中发现了几种致病突变，并且受突变影响的编码蛋白中的特定结构域与相关表型之间的联系已变得明显。靶向KIF5A运动和柄结构域的点突变，预计会损害KIF5A的运动能力，主要与10型痉挛性截瘫（SPG10）和轴索性夏科-马里-图思病（CMT）相关。相反，导致KIF5A尾部延长的翻译移码增强了KIF5A向细胞周边的迁移，诱导驱动蛋白聚集，并与肌萎缩侧索硬化症（ALS）或新生儿难治性肌阵挛（NEIMY）相关。本综述将KIF5A在神经元运输中的结构和作用与其在上述神经退行性和神经发育疾病中的参与联系起来。