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

Abstract 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 fo...

Full description

Saved in:
Bibliographic Details
Main Authors: Marta Cozzi, Barbara Tedesco, Veronica Ferrari, Marta Chierichetti, Paola Pramaggiore, Laura Cornaggia, Rocio Magdalena, Maria Brodnanova, Ali Mohamed, Carmelo Milioto, Margherita Piccolella, Mariarita Galbiati, Paola Rusmini, Valeria Crippa, Cinzia Gellera, Stefania Magri, Franco Taroni, Riccardo Cristofani, Angelo Poletti
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Cell Communication and Signaling
Subjects:
Online Access:https://doi.org/10.1186/s12964-025-02277-x
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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 KIF5A 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.
ISSN:1478-811X