Abstract
KIF1A/UNC-104, a member of the kinesin super family motor proteins, plays 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 DmUNC-104 protein have not been investigated. Here, we prepared recombinant full-length DmUNC-104 protein and determined the biochemical features. We analyzed the effect of a previously identified missense mutation in the FHA domain, called bristly (bris), and found that wild-type DmUNC-104 is a mixture of monomer and dimer and the bris mutation strongly promote the dimerization. Furthermore, we found that disease-associated mutations also promote the dimerization of DmUNC-104. These findings suggest that the FHA domain is essential for the autoinhibition of KIF1A/UNC-104, and that abnormal dimerization of KIF1A is linked to human diseases.
Competing Interest Statement
The authors have declared no competing interest.
