Doublecortin and JIP3 are neural-specific counteracting regulators of dynein-mediated retrograde trafficking.

ABSTRACT: Mutations in the microtubule (MT)-binding protein doublecortin (DCX) or in the MT-based molecular motor dynein result in lissencephaly. However, a functional link between DCX and dynein has not been defined. Here, we demonstrate that DCX negatively regulates dynein-mediated retrograde transport in neurons from Dcx^-/y or Dcx^-/y;Dclk1^-/- mice by reducing dynein's association with MTs and disrupting the composition of the dynein motor complex. Previous work showed an increased binding of the adaptor protein C-Jun-amino-terminal kinase-interacting protein 3 (JIP3) to dynein in the absence of DCX. Using purified components, we demonstrate that JIP3 forms an active motor complex with dynein and its cofactor dynactin with two dyneins per complex. DCX

SUBMITTER: Fu X 

PROVIDER: S-EPMC9799976 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature