Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming.
Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.
Betz
A
A
Max-Planck-Institut, für experimentelle Medizin, Abteilung Neurogenetik, AG Molekulare Neurobiologie, Hermann-Rein-Str. 3, D-37075, Göttingen, Germany.
Thakur
P
P
Junge
H J
HJ
Ashery
U
U
Rhee
J S
JS
Scheuss
V
V
Rosenmund
C
C
Rettig
J
J
Brose
N
N
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers / Q000502:physiology; D020826:rab3A GTP-Binding Protein / Q000378:metabolism
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D020033:Protein Isoforms; C103912:Unc13a protein, rat; D020826:rab3A GTP-Binding Protein