The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis

When nerve terminals in the brain are stimulated, a group of phosphoprotein s called the dephosphins are coordinately dephosphorylated by calcineurin, the Ca2+-dependent protein phosphatase. Amazingly,the seven presently known dephosphins are not structurally related, yet each has been independently shown to be essential for synaptic vesicle endocytosis (SVE). Nowhere else in biology is there a similar example of the coordinated dephosphorylation of such a large group of proteins each sharing roles in the same biological response. This suggests that dephosphorylation and phosphorylation of the dephosphins is essential for SVE. Recent studies in synaptosomes have confi rmed this view, with calcineurin-mediated dephosphorylation of the dephosph ins essential for triggering SVE. The phosphorylation cycle of the dephosph ins might regulate SVE by targeting the proteins to sites of action and by stimulating the assembly of several large essential endocytic protein compl exes.