Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2.
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Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2. / Pechstein, Arndt; Bacetic, Jelena; Vahedi-Faridi, Ardeschir; Brune, Kira; Sundborger, Anna; Tomlin, Nikolay; Krainer, Georg; Vorontsova, Olga; Schäfer, Johannes G; Owe, Simen G; Cousin, Michael A; Saenger, Wolfram; Shupliakov, Oleg; Haucke, Volker.
in: P NATL ACAD SCI USA, Jahrgang 107, Nr. 9, 9, 2010, S. 4206-4211.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2.
AU - Pechstein, Arndt
AU - Bacetic, Jelena
AU - Vahedi-Faridi, Ardeschir
AU - Brune, Kira
AU - Sundborger, Anna
AU - Tomlin, Nikolay
AU - Krainer, Georg
AU - Vorontsova, Olga
AU - Schäfer, Johannes G
AU - Owe, Simen G
AU - Cousin, Michael A
AU - Saenger, Wolfram
AU - Shupliakov, Oleg
AU - Haucke, Volker
PY - 2010
Y1 - 2010
N2 - Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P(2)]-enriched membrane sites within the periactive zone. Such spatiotemporal control is needed to coordinate SV cargo sorting with clathrin/AP2 recruitment and to restrain membrane fission and synaptojanin-mediated uncoating until membrane deformation and clathrin coat assembly are completed. The molecular events underlying these control mechanisms are unknown. Here we show that the endocytic SH3 domain-containing accessory protein intersectin 1 scaffolds the endocytic process by directly associating with the clathrin adaptor AP2. Acute perturbation of the intersectin 1-AP2 interaction in lamprey synapses in situ inhibits the onset of SV recycling. Structurally, complex formation can be attributed to the direct association of hydrophobic peptides within the intersectin 1 SH3A-B linker region with the "side sites" of the AP2 alpha- and beta-appendage domains. AP2 appendage association of the SH3A-B linker region inhibits binding of the inositol phosphatase synaptojanin 1 to intersectin 1. These data identify the intersectin-AP2 complex as an important regulator of clathrin-mediated SV recycling in synapses.
AB - Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P(2)]-enriched membrane sites within the periactive zone. Such spatiotemporal control is needed to coordinate SV cargo sorting with clathrin/AP2 recruitment and to restrain membrane fission and synaptojanin-mediated uncoating until membrane deformation and clathrin coat assembly are completed. The molecular events underlying these control mechanisms are unknown. Here we show that the endocytic SH3 domain-containing accessory protein intersectin 1 scaffolds the endocytic process by directly associating with the clathrin adaptor AP2. Acute perturbation of the intersectin 1-AP2 interaction in lamprey synapses in situ inhibits the onset of SV recycling. Structurally, complex formation can be attributed to the direct association of hydrophobic peptides within the intersectin 1 SH3A-B linker region with the "side sites" of the AP2 alpha- and beta-appendage domains. AP2 appendage association of the SH3A-B linker region inhibits binding of the inositol phosphatase synaptojanin 1 to intersectin 1. These data identify the intersectin-AP2 complex as an important regulator of clathrin-mediated SV recycling in synapses.
KW - Animals
KW - Endocytosis
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Binding Sites
KW - Models, Molecular
KW - Sequence Homology, Amino Acid
KW - Nerve Tissue Proteins/metabolism
KW - Phosphoric Monoester Hydrolases/metabolism
KW - src Homology Domains
KW - Adaptor Protein Complex 2/chemistry/metabolism
KW - Adaptor Proteins, Vesicular Transport/chemistry/metabolism
KW - Lampreys
KW - Synaptic Vesicles/metabolism
KW - Animals
KW - Endocytosis
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Binding Sites
KW - Models, Molecular
KW - Sequence Homology, Amino Acid
KW - Nerve Tissue Proteins/metabolism
KW - Phosphoric Monoester Hydrolases/metabolism
KW - src Homology Domains
KW - Adaptor Protein Complex 2/chemistry/metabolism
KW - Adaptor Proteins, Vesicular Transport/chemistry/metabolism
KW - Lampreys
KW - Synaptic Vesicles/metabolism
M3 - SCORING: Journal article
VL - 107
SP - 4206
EP - 4211
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 9
M1 - 9
ER -