LIS1 regulates cargo-adapter-mediated activation of dynein by overcoming its autoinhibition in vivo.

ABSTRACT: Deficiency of the LIS1 protein causes lissencephaly, a brain developmental disorder. Although LIS1 binds the microtubule motor cytoplasmic dynein and has been linked to dynein function in many experimental systems, its mechanism of action remains unclear. Here, we revealed its function in cargo-adapter-mediated dynein activation in the model organism Aspergillus nidulans Specifically, we found that overexpressed cargo adapter HookA (Hook in A. nidulans) missing its cargo-binding domain (ΔC-HookA) causes dynein and its regulator dynactin to relocate from the microtubule plus ends to the minus ends, and this relocation requires LIS1 and its binding protein, NudE. Astonishingly, the requirement for LIS1 or NudE can be bypassed to a significant extent by mutations that prohibit d

SUBMITTER: Qiu R 

PROVIDER: S-EPMC6829669 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature