PT  - JOURNAL ARTICLE
AU  - Karen Perez de Arce
AU  - Lorena Varela-Nallar
AU  - Olivia Farias
AU  - Alejandra Cifuentes
AU  - Paulina Bull
AU  - Brian A. Couch
AU  - Anthony J. Koleske
AU  - Nibaldo C. Inestrosa
AU  - Alejandra R. Alvarez
TI  - Synaptic Clustering of PSD-95 Is Regulated by c-Abl through Tyrosine Phosphorylation
AID  - 10.1523/JNEUROSCI.2024-09.2010
DP  - 2010 Mar 10
TA  - The Journal of Neuroscience
PG  - 3728--3738
VI  - 30
IP  - 10
4099  - http://www.jneurosci.org/content/30/10/3728.short
4100  - http://www.jneurosci.org/content/30/10/3728.full
SO  - J. Neurosci.2010 Mar 10; 30
AB  - The c-Abl tyrosine kinase is present in mouse brain synapses, but its precise synaptic function is unknown. We found that c-Abl levels in the rat hippocampus increase postnatally, with expression peaking at the first postnatal week. In 14 d in vitro hippocampal neuron cultures, c-Abl localizes primarily to the postsynaptic compartment, in which it colocalizes with the postsynaptic scaffold protein postsynaptic density protein-95 (PSD-95) in apposition to presynaptic markers. c-Abl associates with PSD-95, and chemical or genetic inhibition of c-Abl kinase activity reduces PSD-95 tyrosine phosphorylation, leading to reduced PSD-95 clustering and reduced synapses in treated neurons. c-Abl can phosphorylate PSD-95 on tyrosine 533, and mutation of this residue reduces the ability of PSD-95 to cluster at postsynaptic sites. Our results indicate that c-Abl regulates synapse formation by mediating tyrosine phosphorylation and clustering of PSD-95.