SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice.

ABSTRACT: SLITRK2 is a single-pass transmembrane protein expressed at postsynaptic neurons that regulates neurite outgrowth and excitatory synapse maintenance. In the present study, we report on rare variants (one nonsense and six missense variants) in SLITRK2 on the X chromosome identified by exome sequencing in individuals with neurodevelopmental disorders. Functional studies showed that some variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Strikingly, these variations abolished the ability of SLITRK2 wild-type to reduce the levels of the receptor tyrosine kinase TrkB in neurons. Moreover, Slitrk2 conditional knockout mice exhibited impaired long-term memory and abnormal gait, recapitulating a subset of clinical features of patients with SLITRK2 var

SUBMITTER: El Chehadeh S 

PROVIDER: S-EPMC9287327 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature