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

Quan, Annie, Xue, Jing, Wielens, Jerome, Smillie, Karen J., Anggono, Victor, Parker, Michael W., Cousin, Michael A., Graham, Mark E., Robinson, Phillip J.
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.10 pp. 3760-3765
endocytosis, morphogenesis, mutation, nerve tissue, neurons, phosphorylation
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 α-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 α-helix interactions and stability within the folded F-BAR domain.