Article abstract
Nature Neuroscience 10, 301 - 310 (2007)
Published online: 18 February 2007 | doi:10.1038/nn1858
Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation
Inmaculada Segura1,2, Clara L Essmann1,2, Stefan Weinges1,2 & Amparo Acker-Palmer1
Abstract
Dendritic spines are small protrusions emerging from dendrites that receive excitatory input. The process of spine morphogenesis occurs both in the developing brain and during synaptic plasticity. Molecules regulating the cytoskeleton are involved in spine formation and maintenance. Here we show that reverse signaling by the transmembrane ligands for Eph receptors, ephrinBs, is required for correct spine morphogenesis. The molecular mechanism underlying this function of ephrinBs involves the SH2 and SH3 domain–containing adaptor protein Grb4 and the G protein–coupled receptor kinase–interacting protein (GIT) 1. Grb4 binds by its SH2 domain to Tyr392 in the synaptic localization domain of GIT1. Phosphorylation of Tyr392 and the recruitment of GIT1 to synapses are regulated by ephrinB activation. Disruption of this pathway in cultured rat hippocampal neurons impairs spine morphogenesis and synapse formation. We thus show an important role for ephrinB reverse signaling in spine formation and have mapped the downstream pathway involved in this process.
- Max-Planck Institute of Neurobiology, Am Klopferspitz 18, D-82152 Martinsried, Germany.
- These authors contributed equally to this work.
Correspondence to: Amparo Acker-Palmer1 e-mail: palmer@neuro.mpg.de
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Ephrins keep dendritic spines in shapeNature Neuroscience News and Views (01 Feb 2003)
How ephrins sculpt dendritic spinesNature Neuroscience News and Views (01 Nov 2002)
See all 6 matches for News And ViewsRESEARCH
Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanismNature Neuroscience Article (01 Jan 2007)
Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptorsNature Neuroscience Article
See all 60 matches for Research