RT Journal Article
SR Electronic
T1 A kinesin-1 variant reveals motor-induced microtubule damage in cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.19.464974
DO 10.1101/2021.10.19.464974
A1 Breane G. Budaitis
A1 Somayesadat Badieyan
A1 Yang Yue
A1 T. Lynne Blasius
A1 Dana N. Reinemann
A1 Matthew J. Lang
A1 Michael A. Cianfrocco
A1 Kristen J. Verhey
YR 2021
UL http://biorxiv.org/content/early/2021/10/20/2021.10.19.464974.abstract
AB Kinesins drive the transport of cellular cargoes as they walk along microtubule tracks, however, recent work has suggested that the physical act of kinesins walking along microtubules can stress the microtubule lattice. Here, we describe a kinesin-1 KIF5C mutant with an increased ability to generate defects in the microtubule lattice as compared to the wild-type motor. Expression of the mutant motor in cultured cells resulted in microtubule breakage and fragmentation, suggesting that kinesin-1 variants with increased damage activity would have been selected against during evolution. The increased ability to damage microtubules is not due to the altered motility properties of the mutant motor as expression of the kinesin-3 motor KIF1A, which has similar single-motor motility properties, also caused increased microtubule pausing, bending, and buckling but not breakage. In cells, motor-induced microtubule breakage could not be prevented by increased a-tubulin K40 acetylation, a post-translational modification known to increase microtubule flexibility. In vitro, lattice damage induced by wild-type KIF5C was repaired by soluble tubulin and resulted in increased rescues and microtubule growth whereas lattice damage induced by the KIF5C mutant resulted in larger repair sites that made the microtubule vulnerable to breakage and fragmentation when under mechanical stress. These results demonstrate that kinesin-1 motility causes defects in and damage to the microtubule lattice in cells. While cells have the capacity to repair lattice damage, conditions that exceed this capacity result in microtubule breakage and fragmentation and may contribute to human disease.Competing Interest StatementThe authors have declared no competing interest.