title: A protein interaction node at the neurotransmitter release site: domains of Aczonin/Piccolo, Bassoon, CAST, and rim converge on the N-terminal domain of Munc13-1.
abstract: Multidomain scaffolding proteins organize the molecular machinery of neurotransmitter vesicle dynamics during synaptogenesis and synaptic activity. We find that domains of five active zone proteins converge on an interaction node that centers on the N-terminal region of Munc13-1 and includes the zinc-finger domain of Rim1, the C-terminal region of Bassoon, a segment of CAST1/ELKS2, and the third coiled-coil domain (CC3) of either Aczonin/Piccolo or Bassoon. This multidomain complex may constitute a center for the physical and functional integration of the protein machinery at the active zone. An additional connection between Aczonin and Bassoon is mediated by the second coiled-coil domain of Aczonin. Recombinant Aczonin-CC3, expressed in cultured neurons as a green fluorescent protein fusion protein, is targeted to synapses and suppresses vesicle turnover, suggesting involvements in synaptic assembly as well as activity. Our findings show that Aczonin, Bassoon, CAST1, Munc13, and Rim are closely and multiply interconnected, they indicate that Aczonin-CC3 can actively participate in neurotransmitter vesicle dynamics, and they highlight the N-terminal region of Munc13-1 as a hub of protein interactions by adding three new binding partners to its mechanistic potential in the control of synaptic vesicle priming.
authors.affiliation: Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Agata
authors.initials: A
authors.lastname: Zieba
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Neumann
authors.forename: Monika
authors.initials: M
authors.lastname: Kasper-Sonnenberg
authors.forename: Annegret
authors.initials: A
authors.lastname: Honsbein
authors.forename: Greta
authors.initials: G
authors.lastname: Hultqvist
authors.forename: Tim
authors.initials: T
authors.lastname: Conze
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Witt
authors.forename: Christoph
authors.initials: C
authors.lastname: Limbach
authors.forename: Matthis
authors.initials: M
authors.lastname: Geitmann
authors.forename: Helena
authors.initials: H
authors.lastname: Danielson
authors.forename: Richard
authors.initials: R
authors.lastname: Kolarow
authors.forename: Gesa
authors.initials: G
authors.lastname: Niemann
authors.forename: Volkmar
authors.initials: V
authors.lastname: Lessmann
authors.forename: Manfred W
authors.initials: MW
authors.lastname: Kilimann
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; C512841:Abca4 protein, mouse; C498441:Bsn protein, mouse; D003598:Cytoskeletal Proteins; C505599:Erc2 protein, mouse; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C498631:Pclo protein, mouse; C503321:Unc13a protein, mouse