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Formation of neuronal synapses by ligand-mediated cell adhesion

The GDNF receptor GFR1 is enriched at pre and postsynaptic compartments in hippocampal neurons, suggesting that it could participate in synapse formation. GDNF triggered trans-homophilic binding between GFR?1 molecules, and cell adhesion between GFR?1-expressing cells. In the presence of GDNF, immobilized GFR?1 induced localized presynaptic differentiation in hippocampal and cortical neurons as visualized by clustering of vesicular presynaptic proteins and neurotransmitter transporters. Presynaptic differentiation induced by GDNF was markedly reduced in neurons lacking GFR?1, and hippocampal synapses in Gdnf mutant mice showed reduced incorporation of presynaptic proteins, suggesting a role for GDNF signaling in hippocampal synaptogenesis in vivo. We propose that GFR?1 functions as a LICAM to establish precise synaptic contacts and induce presynaptic differentiation.

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Karolinska Institute
Berzelius väg 35 - Box 285
17177 Stockholm
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