Functional Interaction of the Active Zone Proteins Munc13-1 and RIM1 in Synaptic Vesicle Priming

Betz, Andrea; Thakur, Pratima; Junge, Harald J.; Ashery, Uri; Rhee, Jeong Seop; Scheuss, Volker; Rosenmund, Christian; Rettig, Jens; Brose, Nils

doi:10.1016/s0896-6273(01)00272-0

Cited by 387 publications

(455 citation statements)

References 36 publications

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“…It does not seem to target N-type to the presynaptic nerve terminal. 125,126 RIM possesses an N-terminal domain that binds to Rab3, 127 and two C2 domains C2A and C2B similar to those found in synaptotagmin I, indicating it may be a calcium sensor. 122 This C2 domain can selectively associate with SNAP-25 or synaptotagmin I in a calcium-dependent manner (favoring synaptotagmin I binding at concentrations higher than 75 μM).…”

Section: Functional Interactions Of Presynaptic Calcium Channels Withmentioning

confidence: 92%

Old proteins, developing roles: The regulation of calcium channels by synaptic proteins

Davies

Zamponi²

2008

Channels

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Section: Functional Interactions Of Presynaptic Calcium Channels Withmentioning

confidence: 92%

Old proteins, developing roles: The regulation of calcium channels by synaptic proteins

Davies

Zamponi²

2008

Channels

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“…Another candidate for the displacement of n-sec1 from syntaxin is munc-13, which acts at the priming stage of exocytosis (23), during which loose SNARE complexes form (24,25). Munc-13 has also been shown to functionally interact with the Rab3 effector RIM1, which could provide a link between tethering and SNARE complex formation (26). A brain-specific protein named m-tomosyn (27,28), which binds to syntaxin via a VAMP-like coil domain in its C terminus (29), has also recently been proposed to trigger the removal of n-sec1 from syntaxin, thereby regulating formation of the synaptic SNARE complex (27).…”

mentioning

confidence: 99%

Amisyn, a Novel Syntaxin-binding Protein That May Regulate SNARE Complex Assembly

Scales

Hesser

Masuda

et al. 2002

Journal of Biological Chemistry

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The regulation of SNARE complex assembly likely plays an important role in governing the specificity as well as the timing of membrane fusion. Here we identify a novel brain-enriched protein, amisyn, with a tomosynand VAMP-like coiled-coil-forming domain that binds specifically to syntaxin 1a and syntaxin 4 both in vitro and in vivo, as assessed by co-immunoprecipitation from rat brain. Amisyn is mostly cytosolic, but a fraction cosediments with membranes. The amisyn coil domain can form SNARE complexes of greater thermostability than can VAMP2 with syntaxin 1a and SNAP-25 in vitro, but it lacks a transmembrane anchor and so cannot act as a v-SNARE in this complex. The amisyn coil domain prevents the SNAP-25 C-terminally mediated rescue of botulinum neurotoxin E inhibition of norepinephrine exocytosis in permeabilized PC12 cells to a greater extent than it prevents the regular exocytosis of these vesicles. We propose that amisyn forms nonfusogenic complexes with syntaxin 1a and SNAP-25, holding them in a conformation ready for VAMP2 to replace it to mediate the membrane fusion event, thereby contributing to the regulation of SNARE complex formation.The exocytosis of synaptic and dense core vesicles with the plasma membrane in neurons and neuroendocrine cells requires proteins of the SNARE 1 families. The vesicle-associated membrane protein, VAMP2, a v-or R-SNARE, forms a specific SNARE complex with the target membrane-associated t-or Q-SNAREs syntaxin 1 and SNAP-25, whose parallel orientation brings the two membranes in close enough proximity to fuse (1, 2). Structurally the SNARE complex is a four-helix bundle comprised of one coiled-coil-forming domain from each of syntaxin and VAMP and two from 4). The center of the bundle is made up of 15 hydrophobic layers from the "a" and "d" positions of the heptad repeats of these coiled-coilforming domains, whereas the central "ionic" layer is highly conserved and polar in nature, containing a glutamine residue in the three t-SNAREs and an arginine in the v-SNARE (3), hence the classification of v-and t-SNAREs as R-and QSNAREs, respectively (5). The parallel orientation and high stability of the SNARE bundle led to the proposal that its formation drives the mixing of the membrane bilayers by zippering up through the transmembrane domains of syntaxin and VAMP (1, 2), and there is some evidence to support this (6 -9). After the fusion event, the SNAREs are in a cis-complex in the same membrane and must be dissociated by the action of the ATPase NSF and ␣-SNAP, so that SNAREs can be regenerated for the next round of fusion (10 -13).In addition to mediating the fusion event, the SNARE proteins have also been implicated in the specificity of membrane fusion, the SNARE hypothesis stating that a particular v-SNARE on a transport vesicle should only form a specific complex with its cognate t-SNARE on the correct target membrane, thereby ensuring that the vesicles only fuse with the right compartment (14). Although this hypothesis was cast into doubt by the finding that soluble ...

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“…RIM1-alpha, the best studied isoform, is located at the active zone of the presynaptic terminals and forms a protein scaffold interacting with key presynaptic molecules. In addition to Rab3a, RIM1-alpha binds active zone proteins Munc13-1 147,148 and ERCs, 149,150 the synaptic vesicle protein synaptotagmin1, a calcium sensor for fast synchronous release, 151,152 and other synaptic proteins as alpha-liprins. 152 Indirectly, RIM1-alpha binds to L-type calcium channels 153 through the so-called RIM-BPs (RIM binding proteins).…”

Section: Rim1-alphamentioning

confidence: 99%

“…They did not show any structural abnormalities in the brain and did not have significant changes in the levels of synaptic proteins, except for the active zone protein Munc13-1 which was decreased by B60% probably because, since Munc-13 binds to RIM1-alpha, it degrades when RIM1-alpha is absent. 147,157 Schoch et al systematically studied synaptic transmission at Schaffer collateral/commissural fibers excitatory synapses on CA1 pyramidal cells on hippocampal slices from RIM1-alpha knockout mice and compared it in parallel with available Rab3A homozygous and Munc13-1 heterozygous knockout mice. Rab3A and Munc13-1 interact with RIM1-alpha.…”

Section: Rim1-alphamentioning

confidence: 99%

Active zones for presynaptic plasticity in the brain

García-Junco-Clemente

Linares-Clemente

Fernández‐Chacón

2005

Mol Psychiatry

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Some of the most abundant synapses in the brain such as the synapses formed by the hippocampal mossy fibers, cerebellar parallel fibers and several types of cortical afferents express presynaptic forms of long-term potentiation (LTP), a putative cellular model for spatial, motor and fear learning. Those synapses often display presynaptic mechanisms of LTP induction, which are either NMDA receptor independent of dependent of presynaptic NMDA receptors. Recent investigations on the molecular mechanisms of neurotransmitter release modulation in short-and long-term synaptic plasticity in central synapses give a preponderant role to active zone proteins as Munc-13 and RIM1-alpha, and point toward the maturation process of synaptic vesicles prior to Ca 2 þ -dependent fusion as a key regulatory step of presynaptic plasticity.

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Functional Interaction of the Active Zone Proteins Munc13-1 and RIM1 in Synaptic Vesicle Priming

Cited by 387 publications

References 36 publications

Old proteins, developing roles: The regulation of calcium channels by synaptic proteins

Old proteins, developing roles: The regulation of calcium channels by synaptic proteins

Amisyn, a Novel Syntaxin-binding Protein That May Regulate SNARE Complex Assembly

Active zones for presynaptic plasticity in the brain

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