Here's an article that talks about the role that methylated PP2A can have in dephosphorylating tau and also in reducing the cleavage of amyloid precursor protein, by beta-secretase into Abeta1-42 The authors say that the methylation of Balpha actually governs the way Balpha and the other subunits come together, and the change in the subunit composition apparently changes the substrate-specificity of PP2A in a way that allows PP2A to dephosphorylate tau. I'd been thinking that Balpha was incorporated into PP2A and then methylated, but apparently it's the case that Balpha is methylated before it associates with other subunits. The methylation of the Balpha subunit allows methylated Balpha to associate with other types of PP2A subunits and form heterotrimers, and the heterotrimeric, methylated-Balpha-containing form of PP2A is the one that's most active in dephosphorylating tau.
It's more complicated than I thought it was. They say that APP phosphorylation can enhance soluble APPalpha (sAPPalpha) and APPbeta (sAPPbeta) and be amyloidogenic under some circumstances. The authors also say that methylation of PP2A can help to dephosphorylate APP and thereby reduce the amyloidogenic APP cleavage into Abeta1-40 and Abeta1-42 (under some circumstances). It's important to remember that it's just one mechanism, but it's interesting. It looks like there's a lot of research, now, on the effects that methyltransferases can have on traditional, Alzheimer's-associated processes:
http://www.jneurosci.org/cgi/content/full/27/11/2751
(pubmed: http://www.ncbi.nlm.nih.gov/pubmed/17360897)
No comments:
Post a Comment