Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs regulates membrane tubulation

作者：Quana Annie; Xue Jing; Wielens Jerome; Smillie Karen J; Anggono Victor; Parker Michael W; Cousin Michael A; Graham Mark E; Robinson Phillip J^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(10): 3760-3765.

DOI：10.1073/pnas.1108294109

Syndapin I (PACSIN 1) is a synaptically enriched membrane tubulating protein that plays important roles in activity-dependent bulk endocytosis and neuronal morphogenesis. While syndapin I is an in vitro phosphoprotein, it is not known to be phosphorylated in neurons. Here, we report the identification of two phosphorylation sites, S76 and T181, of syndapin I from nerve terminals. Both residues are located at the N-terminal helix-capping motifs (N-Cap) of different a-helices in the F-BAR domain, important for F-BAR homodimer curvature and dimer-dimer filament assembly, respectively. Phospho-mimetic mutations of these residues regulate lipid-binding and tubulation both in vitro and in cells. Neither phosphosite regulated syndapin I function in activity-dependent bulk endocytosis. Rather, T181 phosphorylation was developmentally regulated and inhibited syndapin I function in neuronal morphogenesis. This suggests a novel mechanism for phosphorylation control of an F-BAR function through the regulation of a-helix interactions and stability within the folded F-BAR domain.

• 出版日期2012-3-6