Semaphorin3F Drives Dendritic Spine Pruning through Rho-GTPase Signaling
Autor: | Sarah D. Wade, Patricia F. Maness, Alexander Kampov-Polevoi, Brenda Temple, Vishwa Mohan, Young K. Truong, Bryce W. Duncan |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
rho GTP-Binding Proteins Dendritic spine Dendritic Spines Neuroscience (miscellaneous) Nerve Tissue Proteins GTPase LIMK1 Biology Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Semaphorin Semaphorin-3F Animals Humans Cells Cultured Neurons Actin remodeling Membrane Proteins Actin cytoskeleton Spine (zoology) Mice Inbred C57BL 030104 developmental biology HEK293 Cells Neurology nervous system Excitatory postsynaptic potential Signal transduction Neuroscience 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Mol Neurobiol |
Popis: | Dendritic spines of cortical pyramidal neurons are initially overproduced then remodeled substantially in the adolescent brain to achieve appropriate excitatory balance in mature circuits. Here we investigated the molecular mechanism of developmental spine pruning by Semaphorin 3F (Sema3F) and its holoreceptor complex, which consists of immunoglobulin-class adhesion molecule NrCAM, Neuropilin-2 (Npn2), and PlexinA3 (PlexA3) signaling subunits. Structure-function studies of the NrCAM-Npn2 interface showed that NrCAM stabilizes binding between Npn2 and PlexA3 necessary for Sema3F-induced spine pruning. Using a mouse neuronal culture system, we identified a dual signaling pathway for Sema3F-induced pruning, which involves activation of Tiam1-Rac1-PAK1-3 -LIMK1/2-Cofilin1 and RhoA-ROCK1/2-Myosin II in dendritic spines. Inhibitors of actin remodeling impaired spine collapse in the cortical neurons. Elucidation of these pathways expands our understanding of critical events that sculpt neuronal networks and may provide insight into how interruptions to these pathways could lead to spine dysgenesis in diseases such as autism, bipolar disorder, and schizophrenia. |
Databáze: | OpenAIRE |
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