PubAg

Main content area

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

Author:
Quan, Annie, Xue, Jing, Wielens, Jerome, Smillie, Karen J., Anggono, Victor, Parker, Michael W., Cousin, Michael A., Graham, Mark E., Robinson, Phillip J.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.10 pp. 3760-3765
ISSN:
0027-8424
Subject:
endocytosis, morphogenesis, mutation, nerve tissue, neurons, phosphorylation
Abstract:
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.
Agid:
413851