Author response: RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses

Brockmann, Marisa M; Maglione, Marta; Willmes, Claudia; Stumpf, Alexander; Bouazza, Boris A; Moreno-Velasquez, Laura; Grauel, M. Katharina; Beed, Prateep; Lehmann, Martin; Gimber, Niclas; Schmoranzer, Jan; Sigrist, Stephan J.; Rosenmund, Christian; Schmitz, Dietmar

doi:10.7554/elife.43243.030

2019

DOI: 10.7554/elife.43243.030

|View full text |Cite

Author response: RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses

Marisa M Brockmann

Marta Maglione

Claudia Willmes

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2020

2021

Publication Types

Select...

Preprint3

Relationship

Self Cite1

Independent2

Authors

Journals

Cited by 3 publications

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Molecular and functional architecture of striatal dopamine release sites

Banerjee

Imig

Balakrishnan

et al. 2020

Preprint

View full text Add to dashboard Cite

Dopamine controls striatal circuit function, but its transmission mechanisms are not well understood. We recently showed that dopamine secretion requires RIM, suggesting that it occurs at active zone-like sites similar to conventional synapses. Here, we establish using a systematic conditional gene knockout approach that Munc13 and Liprin-α, active zone proteins for vesicle priming and release site organization, are important for dopamine secretion. Correspondingly, RIM zinc finger and C2B domains, which bind to Munc13 and Liprin-α, respectively, are needed to restore dopamine release in RIM knockout mice. In contrast, and different from conventional synapses, the active zone scaffolds RIM-BP and ELKS, and the RIM domains that bind to them, are expendable. Hence, dopamine release necessitates priming and release site scaffolding by RIM, Munc13, and Liprin-α, but other active zone proteins are dispensable. Our work establishes that molecularly simple but efficient release site architecture mediates fast dopamine exocytosis.

show abstract

Molecular and functional architecture of striatal dopamine release sites

Banerjee

Imig

Balakrishnan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

Functional architecture of the synaptic transducers at a central glutamatergic synapse

Brockmann

Toulmé

Grasskamp

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

SummaryNeuronal synapses transduce information via the consecutive action of three transducers: voltage-gated Ca2+-channels, fusion-competent synaptic vesicles, and postsynaptic receptors. Their physical distance is thought to influence the speed and efficiency of neurotransmission. However, technical limitations have hampered resolving their nanoscale arrangement. Here, we developed a new method for live-labeling proteins for electron microscopy (EM), revealing that release-competent vesicles preferentially align with Ca2+-channels and postsynaptic AMPA receptors within 20-30 nm and thereby forming a transsynaptic tripartite nanocomplex. Using functional EM, we show that single action potentials cause vesicles within the nanocomplex to fuse with a 50% probability. The loss of the presynaptic scaffold disrupts the formation of the tripartite transducers. Strikingly, the forced transsynaptic alignment of the Ca2+-channel subunit α2δ1 and AMPA receptors suffice to restore neurotransmission in a scaffold lacking synapse. Our results demonstrate a synaptic transducer nanocomplex that actively contributes to the organization of central synapses.

show abstract

RIM and RIM-binding protein localize synaptic CaV2 channels to differentially regulate transmission in neuronal circuits

Jánosi

et al. 2021

Preprint

View full text Add to dashboard Cite

Synapses are intricately organized subcellular compartments in which molecular machines cooperate to ensure spatiotemporally precise transmission of chemical signals. Key components of this machinery are voltage-gated Ca2+-channels (VGCCs), that translate electrical signals into a trigger for fusion of synaptic vesicles (SVs) with the plasma membrane. The VGCCs and the Ca2+ microdomains they generate must be located in the right distance to the primed SV, to elicit transmitter release without delay. Rab3 interacting molecule (RIM) and RIM-binding protein (RIM-BP) were shown in different systems to contribute to the spatial organization of the active zone protein scaffold, and to localize VGCCs next to docked SVs by binding to each other and to the C-terminal region of the Cav2 VGCC α-subunit. We asked how this machinery is organized at the neuromuscular junction (NMJ) of Caenorhabditis elegans, and whether it can differentially regulate transmission in circuits composed of different neuron types. rimb-1 mutants had mild synaptic defects, through loosening the anchoring of the UNC-2 VGCC and delaying the onset of SV fusion, while RIM deletion had much more severe defects. rimb-1 mutants caused increased cholinergic but reduced GABAergic transmission, while overall transmission at the NMJ was reduced, as shown by voltage imaging. The UNC-2 channel could further be untethered by removing its C-terminal PDZ binding motif, and this untethering could be exacerbated by combining the ΔPDZ mutant with the rimb-1 mutation. Similar phenotypes resulted from acute degradation of the UNC-2 β-subunit, indicating that destabilization of the VGCC complex causes the same phenotypes as its untethering.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Author response: RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses

Cited by 3 publications

References 0 publications

Molecular and functional architecture of striatal dopamine release sites

Molecular and functional architecture of striatal dopamine release sites

Functional architecture of the synaptic transducers at a central glutamatergic synapse

RIM and RIM-binding protein localize synaptic CaV2 channels to differentially regulate transmission in neuronal circuits

Contact Info

Product

Resources

About