The RacGAP β-Chimaerin Selectively Mediates Stereotyped Hippocampal Axonal Pruning

• Published in: Cell Vol. 149; no. 7; pp. 1594 - 1606
• Main Authors: Riccomagno, Martin M., Hurtado, Andrés, Wang, HongBin, Macopson, Joshua G. J., Griner, Erin M., Betz, Andrea, Brose, Nils, Kazanietz, Marcelo G., Kolodkin, Alex L.
• Format: Journal Article
• Language: English
• Published: 22.06.2012
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2012.05.018

Axon pruning and synapse elimination are critical for establishing neural connectivity and synaptic plasticity. Stereotyped pruning of axons that originate in the hippocampal dentate gyrus (DG) and extend in 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. However, the signaling events that regulate IPT pruning are not known. We find that inhibition of the small G-protein Rac1 by the Rac GTPase activating protein (GAP) β2-Chimaerin (β2Chn) is essential for Sema3F-mediated IPT pruning. β2Chn selectively binds to the Sema3F receptor neuropilin-2. Sema3F activation of β2Chn is necessary for pruning both in vitro and in vivo , but is dispensable for axon repulsion and spine remodeling. Therefore, β2Chn contributes to a mechanistic distinction among DG axon pruning, repulsion, and dendritic spine remodeling, all mediated by the repellent Sema3F.