title: Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs regulates membrane tubulation.
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.
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, University of Sydney, Wentworthville, New South Wales 2145, Australia.
authors.forename: Annie
authors.initials: A
authors.lastname: Quan
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Jerome
authors.initials: J
authors.lastname: Wielens
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Smillie
authors.forename: Victor
authors.initials: V
authors.lastname: Anggono
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cousin
authors.forename: Mark E
authors.initials: ME
authors.lastname: Graham
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000502:physiology; D020816:Amino Acid Motifs; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004705:Endocytosis; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008051:Lipid Bilayers; D008055:Lipids; C492182:PACSIN1 protein, human; C117738:Pacsin1 protein, rat; D010750:Phosphoproteins