Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Mar 1;136(5):jcs260742.
doi: 10.1242/jcs.260742. Epub 2023 Jan 19.

Insight into the regulation of axonal transport from the study of KIF1A-associated neurological disorder

Kyoko Chiba  1 , Tomoki Kita  2 , Yuzu Anazawa  3 , Shinsuke Niwa  1   2   3
Affiliations
Review

Insight into the regulation of axonal transport from the study of KIF1A-associated neurological disorder

Kyoko Chiba et al. J Cell Sci. .

Abstract

Neuronal function depends on axonal transport by kinesin superfamily proteins (KIFs). KIF1A is the molecular motor that transports synaptic vesicle precursors, synaptic vesicles, dense core vesicles and active zone precursors. KIF1A is regulated by an autoinhibitory mechanism; many studies, as well as the crystal structure of KIF1A paralogs, support a model whereby autoinhibited KIF1A is monomeric in solution, whereas activated KIF1A is dimeric on microtubules. KIF1A-associated neurological disorder (KAND) is a broad-spectrum neuropathy that is caused by mutations in KIF1A. More than 100 point mutations have been identified in KAND. In vitro assays show that most mutations are loss-of-function mutations that disrupt the motor activity of KIF1A, whereas some mutations disrupt its autoinhibition and abnormally hyperactivate KIF1A. Studies on disease model worms suggests that both loss-of-function and gain-of-function mutations cause KAND by affecting the axonal transport and localization of synaptic vesicles. In this Review, we discuss how the analysis of these mutations by molecular genetics, single-molecule assays and force measurements have helped to reveal the physiological significance of KIF1A function and regulation, and what physical parameters of KIF1A are fundamental to axonal transport.

Keywords: Axonal transport; KAND; KIF1A; Kinesin; Synaptic vesicles; UNC-104.

PubMed Disclaimer

Conflict of interest statement

Competing interests The authors declare no competing or financial interests.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources

-