ArticleProceedings of the National Academy of Sciences of the United States of America2012
RIM genes differentially contribute to organizing presynaptic release sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Sex-biased transcriptomic landscapes in bipolar disorder: integrating neurobiology and clinical heterogeneity through cross-study meta-analysis.Biology of sex differences · 2026Pooled it
- Identification of a Ste20-like kinase-dependent signaling network orchestrating cytoskeletal and synaptic development of cortical neurons.Cell communication and signaling : CCS · 2026Article
- Article
- Distinct nanoscale architectures of GABAergic inhibitory synapses predict diverse synaptic output.bioRxiv : the preprint server for biology · 2026Article
- Splicing of ultraconserved poison exons controls mitotic fidelity and stem cell viability.bioRxiv : the preprint server for biology · 2026Article
- Targeting beta-2 adrenergic receptor attenuates schizophrenia-like behavioral effects induced by ketamine in mice: cAMP/PKA/BDNF-PEA-3 and RIM-1α signaling pathways involvement.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- An unexpected specialization of the active zone scaffold RIM at high release synapses.bioRxiv : the preprint server for biology · 2026Article
- Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.Developmental neuroscience · 2025Article
- Divergence in expression of a singing-related neuroplasticity gene in the brains of 2 Ficedula flycatchers and their hybrids.G3 (Bethesda, Md.) · 2025Article
- Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons.PLoS biology · 2024Article
- Gene knockout of RNA binding motif 5 in the brain alters RIMS2 protein homeostasis in the cerebellum and Hippocampus and exacerbates behavioral deficits after a TBI in mice.Experimental neurology · 2024Article
- DNA methylation clocks for clawed frogs reveal evolutionary conservation of epigenetic aging.GeroScience · 2024Article
- Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage.Nature communications · 2024Article
- Nanoscaled RIM clustering at presynaptic active zones revealed by endogenous tagging.Life science alliance · 2023Article
- Adipose tissue coregulates cognitive function.Science advances · 2023Article
- Neurexin-3 subsynaptic densities are spatially distinct from Neurexin-1 and essential for excitatory synapse nanoscale organization in the hippocampus.Nature communications · 2023Article
- Developmental emergence of cortical neurogliaform cell diversity.Development (Cambridge, England) · 2023Article
- Aberrant methylation in neurofunctional gene serves as a hallmark of tumorigenesis and progression in colorectal cancer.BMC cancer · 2023Article
- Synaptotagmin-1 is a CaCell reports · 2023Article
- Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Tight coupling of Ca(2+) channels to the presynaptic active zone is critical for fast synchronous neurotransmitter release. RIMs are multidomain proteins that tether Ca(2+) channels to active zones, dock and prime synaptic vesicles for release, and mediate presynaptic plasticity. Here, we use conditional knockout mice targeting all RIM isoforms expressed by the Rims1 and Rims2 genes to examine the contributions and mechanism of action of different RIMs in neurotransmitter release. We show that acute single deletions of each Rims gene decreased release and impaired vesicle priming but did not alter the extracellular Ca(2+)-responsiveness of release (which for Rims gene mutants is a measure of presynaptic Ca(2+) influx). Moreover, single deletions did not affect the synchronization of release (which depends on the close proximity of Ca(2+) channels to release sites). In contrast, deletion of both Rims genes severely impaired the Ca(2+) responsiveness and synchronization of release. RIM proteins may act on Ca(2+) channels in two modes: They tether Ca(2+) channels to active zones, and they directly modulate Ca(2+)-channel inactivation. The first mechanism is essential for localizing presynaptic Ca(2+) influx to nerve terminals, but the role of the second mechanism remains unknown. Strikingly, we find that although the RIM2 C(2)B domain by itself significantly decreased Ca(2+)-channel inactivation in transfected HEK293 cells, it did not rescue any aspect of the RIM knockout phenotype in cultured neurons. Thus, RIMs primarily act in release as physical Ca(2+)-channel tethers and not as Ca(2+)-channel modulators. Different RIM proteins compensate for each other in recruiting Ca(2+) channels to active zones, but contribute independently and incrementally to vesicle priming.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.