Portal de Periódicos da CAPES

Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin

2004; National Academy of Sciences; Volume: 101; Issue: 4 Linguagem: Inglês

10.1073/pnas.0307862100

1091-6490

Kristin Walther, M. Kasim Diril, Nadja Jung, Volker Haucke,

Erythrocyte Function and Pathophysiology

Synaptic vesicle recycling is in part mediated by clathrin-mediated endocytosis. This process involves the coordinated assembly of clathrin and adaptor proteins and the concomitant selection of cargo proteins. Here, we demonstrate that the endocytotic protein stonin 2 localizes to axonal vesicle clusters through its μ-homology domain. Interaction of this domain with synaptotagmin I is sufficient to recruit stonin 2 to the plasmalemma. The N-terminal domain of stonin 2 harbors multiple AP-2-interaction motifs that bind to the clathrin adaptor complex AP-2. These motifs with the consensus sequence WVxF are capable of binding to the α-adaptin ear domain and to μ2. Mutation of the tyrosine motif-binding pocket of μ2 abolishes recognition of the WVxF peptide, suggesting that association with stonin 2 renders AP-2 incompetent to sort tyrosine motif-containing cargo proteins. We hypothesize that stonin 2 may function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling.