Loss of NDR1/2 kinases impairs endomembrane trafficking and autophagy leading to neurodegeneration.

ABSTRACT: Autophagy is essential for neuronal development and its deregulation contributes to neurodegenerative diseases. NDR1 and NDR2 are highly conserved kinases, implicated in neuronal development, mitochondrial health and autophagy, but how they affect mammalian brain development in vivo is not known. Using single and double Ndr1/2 knockout mouse models, we show that only dual loss of Ndr1/2 in neurons causes neurodegeneration. This phenotype was present when NDR kinases were deleted both during embryonic development, as well as in adult mice. Proteomic and phosphoproteomic comparisons between Ndr1/2 knockout and control brains revealed novel kinase substrates and indicated that endocytosis is significantly affected in the absence of NDR1/2. We validated the endocytic prote

SUBMITTER: Rosianu F 

PROVIDER: S-EPMC9711861 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature