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 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.
Original language | English |
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Pages (from-to) | 3760-3765 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences (PNAS) |
Volume | 109 |
Issue number | 10 |
DOIs | |
Publication status | Published - 6 Mar 2012 |
Keywords / Materials (for Non-textual outputs)
- N-TERMINI
- PLASMA-MEMBRANE
- PROTEIN
- INVAGINATION
- SYNAPTIC VESICLE ENDOCYTOSIS
- DYNAMIN
- ALPHA-HELICES
- PACSIN/SYNDAPIN
- DEPHOSPHORYLATION
- ACTIN CYTOSKELETON