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.
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.
Wang
Xiaolu
X
Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.
Hu
Bin
B
Zieba
Agata
A
Neumann
Nicole G
NG
Kasper-Sonnenberg
Monika
M
Honsbein
Annegret
A
Hultqvist
Greta
G
Conze
Tim
T
Witt
Wolfgang
W
Limbach
Christoph
C
Geitmann
Matthis
M
Danielson
Helena
H
Kolarow
Richard
R
Niemann
Gesa
G
Lessmann
Volkmar
V
Kilimann
Manfred W
MW
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
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