Taxonomic distribution of proteins containing MAGUK_N_PEST domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing MAGUK_N_PEST domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Molecular dissociation of the role of PSD-95 in regulating synaptic strength and LTD.

Xu W, Schluter OM, Steiner P, Czervionke BL, Sabatini B, Malenka RC
Neuron. 2008; 57: 248-62

The postsynaptic density protein PSD-95 influences synaptic AMPA receptor (AMPAR)content and may play a critical role in LTD. Here we demonstrate that the effectsof PSD-95 on AMPAR-mediated synaptic responses and LTD can be dissociated. Ourfindings suggest that N-terminal-domain-mediated dimerization is important forPSD-95's effect on basal synaptic AMPAR function, whereas the C-terminal SH(3)-GKdomains are also necessary for localizing PSD-95 to synapses. We identify PSD-95 point mutants (Q15A, E17R) that maintain PSD-95's influence on basal AMPARsynaptic responses yet block LTD. These point mutants increase the proteolysis ofPSD-95 within its N-terminal domain, resulting in a C-terminal fragment thatfunctions as a dominant negative likely by scavenging critical signaling proteinsrequired for LTD. Thus, the C-terminal portion of PSD-95 serves a dual function. It is required to localize PSD-95 at synapses and as a scaffold for signalingproteins that are required for LTD.

PEST sequences and regulation by proteolysis.

Rechsteiner M, Rogers SW
Trends Biochem Sci. 1996; 21: 267-71

In 1986, we proposed that polypeptide sequences enriched in proline (P), glutamicacid (E), serine (S) and threonine (T) target proteins for rapid destruction. Formuch of the past decade there were only sporadic experimental tests of thehypothesis. This situation changed markedly during the past two years with anumber of papers providing strong evidence that PEST regions do, in fact, serveas proteolytic signals. Here, we briefly review the properties of PEST regionsand some interesting examples of the conditional nature of such signals. Most of the article, however, focuses on recent experimental support for the hypothesisand on mechanisms responsible for the rapid degradation of proteins that contain PEST regions.