Wnt-5a/JNK Signaling Promotes the Clustering of PSD-95 in Hippocampal Neurons

Farias GG.; alfaro ie; Cerpa, W.; Grabowski CP; Godoy JA; Bonansco, C.; Inestrosa, NC


During the formation of synapses, specific regions of pre- and postsynaptic cells associate to form a single functional transmission unit. In this process, synaptogenic factors are necessary to modulate pre- and postsynaptic differentiation. In mammals, different Wnt ligands operate through canonical and non-canonical Wnt pathways, and their precise functions to coordinate synapse structure and function in the mature central nervous system are still largely unknown. Here, we studied the effect of difterent Wnt ligands on postsynaptic organization. We found that Wnt-5a induces short term changes in the clustering of PSD-95, without affecting its total levels. Wnt-5a promotes the recruitment of PSD-95 from a diffuse dendritic cytoplasmic pool to form new PSD-95 clusters in dendritic spines. Moreover, Wnt-5a acting as a non-canonical ligand regulates PSD-95 distribution through a JNK-dependent signaling pathway, as demonstrated by using the TAT-TI-JIP peptide in mature hippocampal neurons, Finally, using adult rat hippocampal slices, we found that Wnt-5a modulates glutamatergic synaptic transmission through a postsynaptic mechanism. Our studies indicate that the Wnt-5a/JNK pathway modulates the postsynaptic region of mammalian synapse directing the clustering and distribution of the physiologically relevant scaffold protein, PSD-95. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

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Título según WOS: Wnt-5a/JNK Signaling Promotes the Clustering of PSD-95 in Hippocampal Neurons
Título según SCOPUS: Wnt-5a/JNK signaling promotes the clustering of PSD-95 in hippocampal neurons
Volumen: 284
Número: 23
Editorial: Elsevier
Fecha de publicación: 2009
Página de inicio: 15857
Página final: 15866
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M808986200