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

Annie Quana, Jing Xue, Jerome Wielens, Karen J. Smillie, Victor Anggono, Michael W. Parker, Michael A. Cousin, Mark E. Graham, Phillip J. Robinson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 languageEnglish
Pages (from-to)3760-3765
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Volume109
Issue number10
DOIs
Publication statusPublished - 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

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