 |
|
Title
|
|
A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?
|
|
|
Authors
|
|
I.Dulubova,
X.Lou,
J.Lu,
I.Huryeva,
A.Alam,
R.Schneggenburger,
T.C.Südhof,
J.Rizo.
|
|
|
Ref.
|
|
EMBO J, 2005,
24,
2839-2850.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
alpha-RIMs and Munc13s are active zone proteins that control priming of synaptic
vesicles to a readily releasable state, and interact with each other via their
N-terminal sequences. The alpha-RIM N-terminal sequence also binds to Rab3s
(small synaptic vesicle GTPases), an interaction that regulates presynaptic
plasticity. We now demonstrate that alpha-RIMs contain adjacent but separate
Munc13- and Rab3-binding sites, allowing formation of a tripartite
Rab3/RIM/Munc13 complex. Munc13 binding is mediated by the alpha-RIM zinc-finger
domain. Elucidation of the three-dimensional structure of this domain by NMR
spectroscopy facilitated the design of a mutation that abolishes
alpha-RIM/Munc13 binding. Selective disruption of this interaction in the calyx
of Held synapse decreased the size of the readily releasable vesicle pool. Our
data suggest that the ternary Rab3/RIM/Munc13 interaction approximates synaptic
vesicles to the priming machinery, providing a substrate for presynaptic
plasticity. The modular architecture of alpha-RIMs, with nested binding sites
for Rab3 and other targets, may be a general feature of Rab effectors that share
homology with the alpha-RIM N-terminal sequence.
|
|
|
|