Article abstract
Nature Neuroscience 10, 293 - 300 (2007)
Published online: 18 February 2007 | doi:10.1038/nn1855
GDNF and GFR
1 promote formation of neuronal synapses by ligand-induced cell adhesion
Fernanda Ledda1,2, Gustavo Paratcha1,2, Tatiana Sandoval-Guzmán1 & Carlos F Ibáñez1
Abstract
The establishment of synaptic connections requires precise alignment of pre- and postsynaptic terminals. The glial cell line–derived neurotrophic factor (GDNF) receptor GFR
1 is enriched at pre- and postsynaptic compartments in hippocampal neurons, suggesting that it has a function in synapse formation. GDNF triggered trans-homophilic binding between GFR1 molecules and cell adhesion between GFR1-expressing cells. This represents the first example of a cell-cell interaction being mediated by a ligand-induced cell adhesion molecule (LICAM). In the presence of GDNF, ectopic GFR1 induced localized presynaptic differentiation in hippocampal neurons, as visualized by clustering of vesicular proteins and neurotransmitter transporters, and by activity-dependent vesicle recycling. Presynaptic differentiation induced by GDNF was markedly reduced in neurons lacking GFR1. Gdnf mutant mice showed reduced synaptic localization of presynaptic proteins and a marked decrease in the density of presynaptic puncta, indicating a role for GDNF signaling in hippocampal synaptogenesis in vivo. We propose that GFR1 functions as a LICAM to establish precise synaptic contacts and induce presynaptic differentiation.
- Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
- Laboratory of Molecular and Cellular Neuroscience, Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
Correspondence to: Carlos F Ibáñez1 e-mail: carlos.ibanez@ki.se
Correspondence to: Fernanda Ledda1,2 e-mail: fernanda.ledda@ki.se
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