RRC ID 82512
Author Hatayama M, Katayama KI, Kawahara Y, Matsunaga H, Takashima N, Iwayama Y, Matsumoto Y, Nishi A, Yoshikawa T, Aruga J.
Title SLITRK1-mediated noradrenergic projection suppression in the neonatal prefrontal cortex.
Journal Commun Biol
Abstract SLITRK1 is an obsessive-compulsive disorder spectrum-disorders-associated gene that encodes a neuronal transmembrane protein. Here we show that SLITRK1 suppresses noradrenergic projections in the neonatal prefrontal cortex, and SLITRK1 functions are impaired by SLITRK1 mutations in patients with schizophrenia (S330A, a revertant of Homo sapiens-specific residue) and bipolar disorder (A444S). Slitrk1-KO newborns exhibit abnormal vocalizations, and their prefrontal cortices show excessive noradrenergic neurites and reduced Semaphorin3A expression, which suppresses noradrenergic neurite outgrowth in vitro. Slitrk1 can bind Dynamin1 and L1 family proteins (Neurofascin and L1CAM), as well as suppress Semaphorin3A-induced endocytosis. Neurofascin-binding kinetics is altered in S330A and A444S mutations. Consistent with the increased obsessive-compulsive disorder prevalence in males in childhood, the prefrontal cortex of male Slitrk1-KO newborns show increased noradrenaline levels, and serotonergic varicosity size. This study further elucidates the role of noradrenaline in controlling the development of the obsessive-compulsive disorder-related neural circuit.
Volume 5(1)
Pages 935
Published 2022-9-9
DOI 10.1038/s42003-022-03891-y
PII 10.1038/s42003-022-03891-y
PMID 36085162
PMC PMC9463131
MeSH Axons Humans Infant, Newborn Male Membrane Proteins Nerve Tissue Proteins Neurites Neuronal Outgrowth Norepinephrine* Prefrontal Cortex*
Resource
Human and Animal Cells PC-12(RCB0009) COS-7(RCB0539) 293T(RCB2202)