Molecular basis for dyneinopathies reveals insight into dynein regulation and dysfunction.

ABSTRACT: Cytoplasmic dynein plays critical roles within the developing and mature nervous systems, including effecting nuclear migration, and retrograde transport of various cargos. Unsurprisingly, mutations in dynein are causative of various developmental neuropathies and motor neuron diseases. These 'dyneinopathies' define a broad spectrum of diseases with no known correlation between mutation identity and disease state. To circumvent complications associated with dynein studies in human cells, we employed budding yeast as a screening platform to characterize the motility properties of seventeen disease-correlated dynein mutants. Using this system, we determined the molecular basis for several classes of etiologically related diseases. Moreover, by engineering compensatory mutations, we alleviate

SUBMITTER: Marzo MG 

PROVIDER: S-EPMC6733598 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature