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Nibaldo C. Inestrosa"Role of Wnt Signaling in Synapse Differentiation and Plasticity"

Abstract :

The expression of Wnts ligands and Wnt signaling components in the mature mammalian central nervous system (CNS) suggests that this pathway might play a role in synaptic maintenance, function and connectivity.
We have shown that the activation of the canonical Wnt pathway induces a short-term modulation in the synaptic vesicle cycle, synaptic transmission, synaptic structure and receptor trafficking in mature hippocampal neurons. Activation of the non-canonical pathway, induces rapid changes in the clustering of PSD-95, through a JNK-dependent signaling pathway, indicating that the Wnt/JNK pathway modulates the postsynaptic region of mammalian synapse. Moreover, Wnt-5a increases the level and retention of surface of GABAA receptors as well as the amplitude of GABA current. These results are mediated by an activation of CaMKII and therefore a Wnt/Ca2+pathway. In addition, we found that Wnt-5a ligand increased intracellular calcium concentration in dendritic processes and the amplitude of NMDA spontaneous miniature currents. The increased in amplitude of the fEPSP of hippocampal slices, was prevented by calcium channel blockers. Current studies investigated the possible interaction of Wnt signaling and NO in glutamatérgica synapses.

Selected publications

Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses.Varela-Nallar L, Alfaro IE, Serrano FG, Parodi J, Inestrosa NC. Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21164-9. Epub 2010 Nov 17.
PMID: 21084636 [PubMed - indexed for MEDLINE] Free PMC Article
Wnt-5a modulates recycling of functional GABAA receptors on hippocampal neurons.Cuitino L, Godoy JA, Farías GG, Couve A, Bonansco C, Fuenzalida M, Inestrosa NC. J Neurosci. 2010 Jun 23;30(25):8411-20.
PMID: 20573888 [PubMed - indexed for MEDLINE] Free Article
Emerging roles of Wnts in the adult nervous system.
Inestrosa NC, Arenas E.
Nat Rev Neurosci. 2010 Feb;11(2):77-86. Epub 2009 Dec 16. Review. PMID: 20010950 [PubMed - indexed for MEDLINE]

Nathalie Sans