
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.06.611684
preprint
1
Article
KIF5A regulates axonal repair and time-dependent axonal transport of SFPQ granules and mitochondria in human motor neurons
Guerra San Juan Irune http://orcid.org/0000-0001-6233-6659

Brunner Jessie http://orcid.org/0000-0003-1266-3226

Eggan Kevin
Toonen Ruud F. http://orcid.org/0000-0002-9900-4233

Verhage Matthijs
11 9 2024
2024.09.06.611684https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.06.611684
nihpp-2024.09.06.611684.pdf
Abstract

Mutations in the microtubule binding motor protein, kinesin family member 5A (KIF5A), cause the fatal motor neuron disease, Amyotrophic Lateral Sclerosis. While KIF5 family members transport a variety of cargos along axons, it is still unclear which cargos are affected by KIF5A mutations. We generated KIF5A null mutant human motor neurons to investigate the impact of KIF5A loss on the transport of various cargoes and its effect on motor neuron function at two different timepoints in vitro . The absence of KIF5A resulted in reduced neurite complexity in young motor neurons (DIV14) and significant defects in axonal regeneration capacity at all developmental stages. KIF5A loss did not affect neurofilament transport but resulted in decreased mitochondria motility and anterograde speed at DIV42. More prominently, KIF5A depletion strongly reduced anterograde transport of SFPQ-associated RNA granules in DIV42 motor neuron axons. We conclude that KIF5A most prominently functions in human motor neurons to promote axonal regrowth after injury as well as to anterogradely transport mitochondria and, to a larger extent, SFPQ-associated RNA granules in a time-dependent manner.
==== Body
pmc
