TY - JOUR
T1 - The RacGAP β2-chimaerin selectively mediates axonal pruning in the hippocampus
AU - Riccomagno, Martin M.
AU - Hurtado, Andrés
AU - Wang, Hongbin
AU - MacOpson, Joshua G.J.
AU - Griner, Erin M.
AU - Betz, Andrea
AU - Brose, Nils
AU - Kazanietz, Marcelo G.
AU - Kolodkin, Alex L.
N1 - Funding Information:
We thank Dr. Silvio Gutkind for the RacQL construct, Barbara Smith and the JHU School of Medicine Microscope Facility for assistance with the TEM, and Dr. Michael Greenberg for the pLLX and pLEMPRA vectors. We also thank Drs. Cynthia Duggan, Roman Giger, David Ginty, Randal Hand, Kang Shen, and Marc Tessier-Lavigne for helpful comments on the manuscript and discussions, and we thank members of Kolodkin laboratory for assistance. This work was supported by a postdoctoral fellowship from the National Ataxia Foundation to M.M.R, NIH R01 CA74197 to M.G.K, and NIH RO1 MH59199 to A.L.K. A.L.K. is an investigator of the Howard Hughes Medical Institute.
PY - 2012/6/22
Y1 - 2012/6/22
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2012.05.018
DO - 10.1016/j.cell.2012.05.018
M3 - Article
C2 - 22726444
AN - SCOPUS:84862697934
SN - 0092-8674
VL - 149
SP - 1594
EP - 1606
JO - Cell
JF - Cell
IS - 7
ER -