Open AccessA Kalirin missense mutation enhances dendritic RhoA signaling and leads to regression of cortical dendritic arbors across development
Author(s) -
Melanie Grubisha,
Tao Sun,
Leanna Eisenman,
Susan Erickson,
Shinnyi Chou,
Cassandra Helmer,
Melody Trudgen,
Ying Ding,
Gregg E. Homanics,
Peter Penzes,
Zachary P. Wills,
Robert A. Sweet
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2022546118
Subject(s) - rhoa , missense mutation , dendritic spine , guanine nucleotide exchange factor , biology , neuroscience , cerebral cortex , mutation , gtpase , genetics , signal transduction , hippocampal formation , gene
Significance Dendrites are long branching processes on neurons that contain small processes called spines that are the site of connections with other neurons, establishing cortical circuitry. Dendrites have long been considered stable structures, with rapid growth prior to adolescence followed by maintenance of size into adulthood. However, schizophrenia is characterized by accelerated reductions of cortical gray matter volume and onset of clinical symptoms during adolescence, with reductions in dendritic length present when examined after death. We show that dendrites retain the capacity for regression and that a mild genetic vulnerability in a regression pathway leads to onset of structural impairments in previously formed dendrites across adolescence. This suggests that targeting specific regression pathways could potentially lead to new therapeutics for schizophrenia.