The FHA domain is essential for autoinhibition of KIF1A/UNC-104 proteins.
J Cell Sci
; 137(19)2024 Oct 01.
Article
de En
| MEDLINE
| ID: mdl-39239883
ABSTRACT
KIF1A/UNC-104 proteins, which are members of the kinesin superfamily of motor proteins, play a pivotal role in the axonal transport of synaptic vesicles and their precursors. Drosophila melanogaster UNC-104 (DmUNC-104) is a relatively recently discovered Drosophila kinesin. Although some point mutations that disrupt synapse formation have been identified, the biochemical properties of the DmUNC-104 protein have not been investigated. Here, we prepared recombinant full-length DmUNC-104 protein and determined its biochemical features. We analyzed the effect of a previously identified missense mutation in the forkhead-associated (FHA) domain, called bristly (bris). The bris mutation strongly promoted the dimerization of DmUNC-104 protein, whereas wild-type DmUNC-104 was a mixture of monomers and dimers. We further tested the G618R mutation near the FHA domain, which was previously shown to disrupt the autoinhibition of Caenorhabditis elegans UNC-104. The biochemical properties of the G618R mutant recapitulated those of the bris mutant. Finally, we found that disease-associated mutations also promote the dimerization of DmUNC-104. Collectively, our results suggest that the FHA domain is essential for autoinhibition of KIF1A/UNC-104 proteins, and that abnormal dimerization of KIF1A might be linked to human diseases.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Kinésine
/
Protéines de Drosophila
/
Drosophila melanogaster
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Cell Sci
/
J. cell. sci
/
Journal of cell science
Année:
2024
Type de document:
Article
Pays d'affiliation:
Japon
Pays de publication:
Royaume-Uni