The RacGAP β2-Chimaerin selectively mediates axonal pruning in the hippocampus.
Axon pruning and synapse elimination promote neural connectivity and synaptic plasticity. Stereotyped pruning of axons that originate in the hippocampal dentate gyrus (DG) and extend along the infrapyramidal tract (IPT) occurs during postnatal murine development by neurite retraction and resembles axon repulsion. The chemorepellent Sema3F is required for IPT axon pruning, dendritic spine remodeling, and repulsion of DG axons. The signaling events that regulate IPT axon pruning are not known. We find that inhibition of the small G protein Rac1 by the Rac GTPase-activating protein (GAP) β2-Chimaerin (β2Chn) mediates Sema3F-dependent pruning. The Sema3F receptor neuropilin-2 selectively binds β2Chn, and ligand engagement activates this GAP to ultimately restrain Rac1-dependent effects on cytoskeletal reorganization. β2Chn is necessary for axon pruning both in vitro and in vivo, but it is dispensable for axon repulsion and spine remodeling. Therefore, a Npn2/β2Chn/Rac1 signaling axis distinguishes DG axon pruning from the effects of Sema3F on repulsion and dendritic spine remodeling.
The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Martin M
MM
Riccomagno
Andrés
A
Hurtado
HongBin
H
Wang
Joshua G J
JG
Macopson
Erin M
EM
Griner
Andrea
A
Betz
Nils
N
Brose
Marcelo G
MG
Kazanietz
Alex L
AL
Kolodkin
D000818:Animals; D001369:Axons / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C491229:Sema3f protein, mouse; C079844:beta-chimaerin; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein