The Big Picture of Synaptic Phosphorylation

Science's STKE  22 Feb 2005:
Vol. 2005, Issue 272, pp. tw73
DOI: 10.1126/stke.2722005tw73

Collins et al. have used advances in mass spectrometry and strategies to enrich phosphopeptides in cell extracts to enable proteomic analysis of phosphorylation events in synaptosomes isolated from mouse forebrain. Although phosphorylation events are known to be important in synaptic signaling and many have been studied, the screen suggests that traditional studies have only just scratched the surface. The authors identified almost 300 phosphorylation sites, and 92% of these were not previously described. Many proteins showed multiple phosphorylation sites (as many as 30), so the 300 sites were spread over 79 proteins, half of which were not previously shown to be phosphorylated. The authors used both screens with peptide arrays along with literature mining and bioinformatic analysis to assign kinases likely to regulate the identified sites. Most substrates appear to be targets of multiple kinases. One group of kinases appears to phosphorylate their target proteins on multiple targets, and another appears to use just one site per substrate. A relatively small number of kinases appear to account for much of the phosphorylation observed. In fact, just nine kinases appear to be sufficient to regulate more than 250 of the observed sites. The synaptic phosphoproteome, the authors conclude, reveals a highly interconnected signaling network.

M. O. Collins, L. Yu, M. P. Coba, H. Husi, I. Campuzano, W. P. Blackstock, J. S. Choudhary, S. N. Grant, Proteomic analysis of in vivo phosphorylated synaptic proteins. J. Biol. Chem. 280, 5972-5982 (2005). [Abstract] [Full Text]