INVESTIGADORES
LEDDA Maria Fernanda
congresos y reuniones científicas
Título:
Formation of neuronal synapses by GDNF-induced cell adhesion
Autor/es:
LEDDA, F
Lugar:
Huerta Grande, Cordoba
Reunión:
Congreso; I Reunion Conjunta de Neurociencias IRCN; 2009
Institución organizadora:
Sociedad Argentina de Investigacion en Neurociencias y Taller Argentino de Neurociencias
Resumen:
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The
formation of neuronal synapses involves the precise assembly of the machinery
responsible for neurotransmitter release at the presynaptic side and
recruitment of neurotransmitter receptors to the postsynaptic density (PSD).
Recent evidence indicates that cell adhesion molecules (CAMs) participate prominently
in the key steps of synapse formation, inducing trans-synaptic adhesion and
promoting an accurate alignment of pre- and postsynaptic terminals. The glial
cell line-derived neurotrophic factor (GDNF) receptor GFRα1 is enriched at pre- and
postsynaptic terminals in hippocampal neurons, suggesting that it has a role in
synapse formation. We demonstrate that GDNF triggered trans-homophilic binding
between GFRα1 molecules
and cell adhesion between GFRα1-expressing cells. This represents the first example of a cell-cell
interaction being mediated by ligand-induced cell adhesion molecule (LICAM). In
the presence of GDNF, ectopic GFRα1 induced localize presynaptic differentiation in hippocampal neurons,
as visualized by clustering of vesicular proteins and neurotransmitter
transporters, and by activity-dependent vesicle recycling. Presynaptic
differentiation was markedly reduced in neurons lacking GFRα1. Gdnf mutant mice showed reduced
synaptic localization of presynaptic proteins and a significant decrease in the
density of presynaptic puncta, indicating a role for GDNF signaling in
hippocampal synaptogenesis in vivo. We propose that GFRα1 functions as a LICAM to establish
precise synaptic contacts and induce presynaptic differentiation
