CDK5-dependent activation of dynein in the axon initial segment regulates polarized cargo transport in neurons.

ABSTRACT: The unique polarization of neurons depends on selective sorting of axonal and somatodendritic cargos to their correct compartments. Axodendritic sorting and filtering occurs within the axon initial segment (AIS). However, the underlying molecular mechanisms responsible for this filter are not well understood. Here, we show that local activation of the neuronal-specific kinase cyclin-dependent kinase 5 (CDK5) is required to maintain AIS integrity, as depletion or inhibition of CDK5 induces disordered microtubule polarity and loss of AIS cytoskeletal structure. Furthermore, CDK5-dependent phosphorylation of the dynein regulator Ndel1 is required for proper re-routing of mislocalized somatodendritic cargo out of the AIS; inhibition of this pathway induces profound mis-sorting defects. While i

SUBMITTER: Klinman E 

PROVIDER: S-EPMC5683723 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature