Neurodevelopmental disorder-associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase.

ABSTRACT: Mutations in TAOK1, which encodes a serine-threonine kinase, are associated with both autism spectrum disorder (ASD) and neurodevelopmental delay (NDD). Here, we investigated the molecular function of this evolutionarily conserved kinase and the mechanisms through which TAOK1 mutations may lead to neuropathology. We found that TAOK1 was abundant in neurons in the mammalian brain and remodeled the neuronal plasma membrane through direct association with phosphoinositides. Our characterization of four NDD-associated TAOK1 mutations revealed that these mutants were catalytically inactive and were aberrantly trapped in a membrane-bound state, which induced abnormal membrane protrusions. Expression of these TAOK1 mutants in cultured mouse hippocampal neurons led to abnormal

SUBMITTER: Beeman N 

PROVIDER: S-EPMC9970049 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature