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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.

Pubmed ID: 22726444

Authors

  • Riccomagno MM
  • Hurtado A
  • Wang H
  • Macopson JG
  • Griner EM
  • Betz A
  • Brose N
  • Kazanietz MG
  • Kolodkin AL

Journal

Cell

Publication Data

June 22, 2012

Associated Grants

  • Agency: NINDS NIH HHS, Id: P30 NS050274
  • Agency: NCI NIH HHS, Id: R01 CA74197
  • Agency: NIMH NIH HHS, Id: R01 MH059199
  • Agency: NIMH NIH HHS, Id: R01 MH59199
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Axons
  • Dentate Gyrus
  • Hippocampus
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Neurons
  • Neuropeptides
  • Signal Transduction
  • Synapses
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein