Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis

被引:172
作者
Anggono, Victor
Smillie, Karen J.
Graham, Mark E.
Valova, Valentina A.
Cousin, Michael A.
Robinson, Phillip J.
机构
[1] Childrens Med Res Inst, Cell Signalling Unit, Wentworthville, NSW 2145, Australia
[2] Univ Edinburgh, Membrane Biol Grp, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland
基金
英国惠康基金;
关键词
D O I
10.1038/nn1695
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dynamin I is dephosphorylated at Ser-774 and Ser-778 during synaptic vesicle endocytosis (SVE) in nerve terminals. Phosphorylation was proposed to regulate the assembly of an endocytic protein complex with amphiphysin or endophilin. Instead, we found it recruits syndapin I for SVE and does not control amphiphysin or endophilin binding in rat synaptosomes. After depolarization, syndapin showed a calcineurin-mediated interaction with dynamin. A peptide mimicking the phosphorylation sites disrupted the dynamin-syndapin complex, not the dynamin-endophilin complex, arrested SVE and produced glutamate release fatigue after repetitive stimulation. Pseudophosphorylation of Ser-774 or Ser-778 inhibited syndapin binding without affecting amphiphysin recruitment. Site mutagenesis to alanine arrested SVE in cultured neurons. The effects of the sites were additive for syndapin I binding and SVE. Thus syndapin I is a central component of the endocytic protein complex for SVE via stimulus-dependent recruitment to dynamin I and has a key role in synaptic transmission.
引用
收藏
页码:752 / 760
页数:9
相关论文
共 40 条
  • [21] Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses
    Lee, SY
    Wenk, MR
    Kim, Y
    Naim, AC
    De Camilli, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (02) : 546 - 551
  • [22] CALCINEURIN INHIBITION OF DYNAMIN-I GTPASE ACTIVITY COUPLED TO NERVE-TERMINAL DEPOLARIZATION
    LIU, JP
    SIM, ATR
    ROBINSON, PJ
    [J]. SCIENCE, 1994, 265 (5174) : 970 - 973
  • [23] Regulated interactions between dynamin and the actin-binding protein cortactin modulate cell shape
    McNiven, MA
    Kim, L
    Krueger, EW
    Orth, JD
    Cao, H
    Wong, TW
    [J]. JOURNAL OF CELL BIOLOGY, 2000, 151 (01) : 187 - 198
  • [24] Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins
    Miesenböck, G
    De Angelis, DA
    Rothman, JE
    [J]. NATURE, 1998, 394 (6689) : 192 - 195
  • [25] The large GTPase dynamin regulates actin comet formation and movement in living cells
    Orth, JD
    Krueger, EW
    Cao, H
    McNiven, MA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (01) : 167 - 172
  • [26] BAR domains as sensors of membrane curvature: The amphiphysin BAR structure
    Peter, BJ
    Kent, HM
    Mills, IG
    Vallis, Y
    Butler, PJG
    Evans, PR
    McMahon, HT
    [J]. SCIENCE, 2004, 303 (5657) : 495 - 499
  • [27] Syndapin I, a synaptic dynamin binding protein that associates with the neural Wiskott-Aldrich syndrome protein
    Qualmann, B
    Roos, J
    DiGregorio, PJ
    Kelly, RB
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (02) : 501 - 513
  • [28] The SH3p4/Sh3p8/SH3p13 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain
    Ringstad, N
    Nemoto, Y
    DeCamilli, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (16) : 8569 - 8574
  • [29] DYNAMIN GTPASE REGULATED BY PROTEIN-KINASE-C PHOSPHORYLATION IN NERVE-TERMINALS
    ROBINSON, PJ
    SONTAG, JM
    LIU, JP
    FYKSE, EM
    SLAUGHTER, C
    MCMAHON, H
    SUDHOF, TC
    [J]. NATURE, 1993, 365 (6442) : 163 - 166
  • [30] Actin has a molecular scaffolding, not propulsive, role in presynaptic function
    Sankaranarayanan, S
    Atluri, PP
    Ryan, TA
    [J]. NATURE NEUROSCIENCE, 2003, 6 (02) : 127 - 135