Affinage

RIMS1

Regulating synaptic membrane exocytosis protein 1 · UniProt Q86UR5

Length
1692 aa
Mass
189.1 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RIMS1 (RIM1) is a multidomain presynaptic active zone scaffold protein that serves as a central organizer of neurotransmitter release by tethering synaptic vesicles, recruiting priming factors, and regulating presynaptic calcium channel function. Its N-terminal zinc-finger domain simultaneously binds GTP-Rab3 on synaptic vesicles and Munc13-1, forming a tripartite Rab3/RIM/Munc13 complex that activates Munc13 by disrupting its autoinhibitory homodimer, thereby promoting vesicle docking and priming into a fusion-competent state (PMID:16052212, PMID:16732694, PMID:28489077). RIM1 also clusters and modulates gating of presynaptic voltage-gated Ca²⁺ channels (CaV2.1, CaV2.2, CaV1.4) through its C2 domains and interaction with CaVβ subunits, and its scaffolding connects CAST/ELKS, Bassoon, Piccolo, and liprin-α into the active zone cytomatrix (PMID:11438518, PMID:26400943, PMID:12163476, PMID:23751498). RIM1 protein levels are regulated by SCRAPPER-mediated ubiquitination and proteasomal degradation, providing a mechanism for activity-dependent tuning of synaptic strength, and mutations in the C2A domain (R844H) cause cone-rod dystrophy 7 (CORD7) (PMID:17803915, PMID:12659814).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Identifying RIM1 as a Rab3 effector established that a dedicated active zone protein links GTP-bound vesicle Rabs to the release machinery, answering how vesicles are tethered at release sites.

    Evidence Yeast two-hybrid, GST pull-down, and PC12 cell exocytosis assays

    PMID:10748113

    Open questions at the time
    • Rab3-RIM interaction was shown in vitro and overexpression; in vivo necessity not yet demonstrated at this point
    • Whether other Rab family members use RIM was unresolved
  2. 2001 High

    Demonstrating that RIM1 functionally interacts with Munc13-1 and that C. elegans RIM acts post-docking to regulate syntaxin-dependent priming established RIM as a priming factor rather than merely a vesicle tether.

    Evidence Co-IP and electrophysiology in mammalian neurons; genetic epistasis with syntaxin gain-of-function suppressors and EM in C. elegans

    PMID:11343654 PMID:11559854

    Open questions at the time
    • Structural basis of the RIM-Munc13 interaction was unknown
    • Whether RIM's priming function requires Rab3 binding was not separated
  3. 2001 High

    Mapping RIM1 C2 domain binding to N-type Ca²⁺ channels, SNAP-25, and synaptotagmin-I revealed that RIM directly interfaces with the Ca²⁺-sensing and fusion machinery, not just vesicle tethering.

    Evidence Surface plasmon resonance and mutagenesis with recombinant C2 domains

    PMID:11438518

    Open questions at the time
    • In vivo relevance of C2-channel interaction not demonstrated
    • Whether Ca²⁺ channel binding is direct in neurons or mediated by auxiliary subunits was unclear
  4. 2002 High

    Discovery that CAST directly binds RIM1 and Bassoon, forming a ternary complex, established RIM1 as a hub connecting cytomatrix proteins at the active zone scaffold.

    Evidence Co-IP, yeast two-hybrid, GST pull-down, and immunolocalization; dominant-negative CAST fragments impair transmission

    PMID:12163476 PMID:14734538

    Open questions at the time
    • Whether scaffold assembly is hierarchical or simultaneous was unknown
    • Stoichiometry of the complex at native active zones not determined
  5. 2003 High

    Systematic Rab binding screens and identification of phosphorylation-dependent 14-3-3 binding expanded the regulatory inputs to RIM1, showing it integrates vesicle identity signals and kinase-mediated plasticity signals.

    Evidence Cotransfection with 42 Rabs; CaMKII phosphorylation and mutagenesis of Ser-241/Ser-287

    PMID:12578829 PMID:12871946

    Open questions at the time
    • Physiological role of 14-3-3 binding at synapses not demonstrated
    • Functional consequence of RIM splicing on Rab selectivity in vivo unknown
  6. 2005 High

    NMR structure of the RIM zinc-finger domain bound to Munc13 and Rab3 revealed how adjacent but separate binding sites enable a tripartite Rab3/RIM/Munc13 complex, solving the structural basis for coupling vesicle tethering to priming activation.

    Evidence NMR spectroscopy, mutagenesis, electrophysiology at calyx of Held showing reduced RRP upon disruption

    PMID:16052212

    Open questions at the time
    • Full-length RIM structure not available
    • How the tripartite complex transitions to trigger fusion was unresolved
  7. 2006 High

    Crystal structures of the Munc13 C2A homodimer and C2A/RIM heterodimer revealed a homodimer-to-heterodimer switch mechanism by which RIM activates Munc13, and RIM1α was shown to be required for Munc13 active zone recruitment.

    Evidence X-ray crystallography (1.44–1.78 Å), NMR, mutagenesis; RIM1α KO mice show reduced Munc13-1 at active zones

    PMID:16704978 PMID:16732694

    Open questions at the time
    • Whether this switch is regulated by upstream signals in vivo was unknown
    • Redundancy with RIM2 in Munc13 recruitment not addressed
  8. 2006 High

    High-pressure freeze EM in C. elegans demonstrated that UNC-10/RIM localizes to dense projections and promotes vesicle localization within 30 nm of the active zone membrane independently of UNC-13/Munc13, establishing a Munc13-independent tethering role.

    Evidence Immunogold EM and morphometric analysis in unc-10 and unc-13 mutants

    PMID:16885217

    Open questions at the time
    • Molecular basis of Munc13-independent tethering not identified
    • Whether this mechanism is conserved in mammals was unclear
  9. 2007 High

    Discovery that SCRAPPER ubiquitinates RIM1 for proteasomal degradation provided the first mechanism for activity-dependent regulation of RIM1 abundance and synaptic strength.

    Evidence Ubiquitination assay, Scrapper-KO mice showing increased RIM1 levels and elevated mEPSC frequency, rescued by RIM1 knockdown

    PMID:17803915

    Open questions at the time
    • Whether other E3 ligases target RIM1 was unknown
    • Activity-dependent regulation of SCRAPPER itself not characterized
  10. 2008 High

    Identification of the RIM1β isoform and demonstration that RIM1α/β double knockout abolishes long-term presynaptic plasticity and severely impairs synaptic transmission established that both isoforms are essential and partially redundant.

    Evidence KO mouse generation, electrophysiology comparing single and double deletions

    PMID:19074017

    Open questions at the time
    • Specific non-redundant functions of RIM1β were not delineated
    • Whether RIM1β compensates for RIM1α in Rab3-independent pathways unknown
  11. 2011 High

    Showing that RIM1 associates with CaVβ subunits and slows inactivation of L-type (CaV1.2/1.3) and reduces G-protein inhibition of CaV2.2 channels identified the CaVβ auxiliary subunit as the primary physical link between RIM and calcium channels.

    Evidence Co-IP, patch clamp, siRNA knockdown in insulin-secreting cells; heterologous CaV2.2 expression with opioid receptor activation

    PMID:21331761 PMID:21402706

    Open questions at the time
    • Whether RIM also binds α1 subunits directly in native tissue remained debated
    • Structural basis of RIM-CaVβ interaction not determined
  12. 2013 High

    FRAP experiments showing liprin-α2 recruits RIM1 to presynaptic sites and promotes its dynamic turnover there established liprin-α as an upstream organizer of RIM localization.

    Evidence FRAP, co-IP, liprin-α2 depletion with electrophysiology and ultrastructure

    PMID:23751498

    Open questions at the time
    • Whether liprin-α acts before or in parallel with ELKS for RIM recruitment was unresolved
    • Mechanism of liprin-α-mediated RIM turnover unknown
  13. 2015 High

    Conditional RIM1/2 double knockout from rod photoreceptors nearly abolished Ca²⁺ currents through CaV1.4 without reducing channel expression, definitively separating RIM's role in channel gating from channel localization at ribbon synapses.

    Evidence Conditional KO mice, voltage-clamp recordings from rods, capacitance measurements, immunofluorescence for CaV1.4

    PMID:26400943

    Open questions at the time
    • Molecular mechanism by which RIM facilitates channel gating unknown
    • Whether the gating role extends to conventional synapses not directly tested
  14. 2017 High

    Structure-guided mutagenesis of Munc13 C2A showed the RIM-Munc13 heterodimer is not merely an activating switch but an integral component of the docking and priming machinery.

    Evidence C2A domain mutagenesis disrupting homo- vs heterodimer, EM and electrophysiology in hippocampal cultures

    PMID:28489077

    Open questions at the time
    • Whether heterodimer persists through fusion or disassembles was unknown
    • Role of other Munc13 domains in docking with RIM not addressed
  15. 2019 High

    Demonstrating that the minimal N-terminal RIM1 fragment containing Rab3- and Munc13-binding domains is sufficient to rescue dense-core vesicle exocytosis defined the minimal functional unit for RIM's role in regulated secretion.

    Evidence RIM1/2 conditional KO, Rab3 quadruple KO, live-cell DCV fusion imaging, domain rescue

    PMID:31679900

    Open questions at the time
    • Whether C2 domains contribute to DCV release efficiency not fully resolved
    • Applicability to synaptic vesicle release not directly tested in same system
  16. 2020 High

    Combinatorial knockout of RIM and Munc13-1 separated three distinct RIM functions: Munc13-independent vesicle localization near the membrane, Munc13-dependent vesicle docking/priming, and a unique role in release efficiency.

    Evidence RIM/Munc13-1 KO/KD combinations in hippocampal neurons, EM ultrastructure and electrophysiology

    PMID:33139401

    Open questions at the time
    • Molecular basis of RIM's Munc13-independent vesicle localization not identified
    • Mechanism underlying RIM's unique control of release efficiency unknown
  17. 2021 High

    Endogenous tagging in C. elegans confirmed that UNC-10/RIM and SYD-2/liprin-α cooperate to localize CaV2 channels at presynaptic terminals, extending the channel-positioning role of RIM to an invertebrate system.

    Evidence Endogenous GFP tagging of UNC-2/CaV2, quantitative fluorescence in single and double mutants

    PMID:33975919

    Open questions at the time
    • Whether this involves direct RIM-channel interaction or intermediate scaffolds in C. elegans is unresolved
    • Functional consequences for neurotransmission in these mutant combinations not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: what is the structural basis for RIM's modulation of Ca²⁺ channel gating, how does RIM promote vesicle membrane proximity independently of Munc13, and how are RIM1α and RIM1β differentially regulated to tune distinct forms of presynaptic plasticity.
  • No full-length RIM structure available
  • Mechanism of Munc13-independent vesicle localization by RIM not molecularly defined
  • Differential regulation and non-redundant functions of RIM1α vs RIM1β largely unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3
Complex memberships
CAST/RIM/Bassoon active zone complexRIM/RIM-BP complexRab3/RIM/Munc13 tripartite complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 RIM1 interacts functionally with Munc13-1 at the presynaptic active zone; disruption of this interaction causes loss of fusion-competent synaptic vesicles, phenocopying Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. Co-immunoprecipitation, yeast two-hybrid, electrophysiology in cultured neurons, loss-of-function genetic analysis Neuron High 11343654
2001 C. elegans UNC-10/RIM acts after synaptic vesicle docking (post-docking) to regulate vesicle priming, likely by regulating conformational changes in syntaxin; expression of constitutively open syntaxin suppresses the physiological defects of Rim mutants. Genetic epistasis (rim mutants, syntaxin gain-of-function suppressor), electron microscopy to count docked vesicles, electrophysiology Nature neuroscience High 11559854
2000 RIM1 is a Rab3 effector that binds GTP-bound Rab3 on synaptic vesicles via its N-terminal zinc finger domain; it also binds RIM-binding proteins (RIM-BPs) via a proline-rich sequence between the two C2 domains. RIM2, a second family member, shares the same domain architecture and also regulates exocytosis. Yeast two-hybrid, GST pull-down, in vitro binding assays, exocytosis assay in PC12 cells The Journal of biological chemistry High 10748113
2001 The two C2 domains of RIM bind Ca2+ channel alpha1B subunit (N-type) in a Ca2+-independent manner (EC50 ~20 nM), and also bind SNAP-25 and synaptotagmin-I; synaptotagmin-I binding is Ca2+-dependent and abolished by mutations in positively charged residues in the C2 domains. In vitro binding assays with recombinant C2 domains, surface plasmon resonance, site-directed mutagenesis The Journal of biological chemistry High 11438518
2002 CAST (CAZ-associated structural protein) directly binds RIM1 and indirectly binds Munc13-1 through RIM1, forming a ternary complex; Bassoon also associates with this complex. RIM1 and Bassoon bind directly to distinct regions of CAST. Co-immunoprecipitation, yeast two-hybrid, GST pull-down, immunolocalization The Journal of cell biology High 12163476
2004 CAST serves as a key scaffold at the cytomatrix of the active zone by directly binding RIM1 and Bassoon; microinjection of the RIM1-binding or Bassoon-binding region of CAST impairs synaptic transmission in cultured superior cervical ganglion neurons. GST pull-down, co-immunoprecipitation, microinjection of dominant-negative fragments, electrophysiology The Journal of cell biology High 14734538
2005 Alpha-RIMs (including RIM1) contain adjacent but separate Munc13- and Rab3-binding sites, allowing formation of a tripartite Rab3/RIM/Munc13 complex. The Munc13-binding site resides in the alpha-RIM zinc-finger domain. Disruption of this interaction at the calyx of Held synapse decreased the size of the readily releasable vesicle pool. NMR spectroscopy (structure of zinc-finger domain), site-directed mutagenesis, in vitro binding, electrophysiology at calyx of Held The EMBO journal High 16052212
2006 The Munc13-1 C2A domain homodimerizes and this homodimerization competes with Munc13-1/RIM heterodimer formation. Crystal structures of both the C2A homodimer (1.44 Å) and the C2A/RIM zinc-finger heterodimer (1.78 Å) were determined, revealing the structural basis for the Munc13-1 homodimer-to-heterodimer switch. X-ray crystallography, NMR spectroscopy, mutagenesis PLoS biology High 16732694
2006 RIM1alpha binding to Munc13-1 and ubMunc13-2 is required for their active zone recruitment; a single point mutation (I121N) in Munc13-1 abolishes RIM1alpha binding and prevents efficient recruitment of ubMunc13-2 to synapses. RIM1alpha-deficient brain shows decreased Munc13-1 levels and loss of Munc13-1 enrichment at mossy fiber active zones. Site-directed mutagenesis, co-immunoprecipitation, immunofluorescence, RIM1alpha knockout mice The Journal of biological chemistry High 16704978
2007 SCRAPPER, a synapse-localized E3 ubiquitin ligase, directly binds and ubiquitinates RIM1, leading to its proteasomal degradation. In Scrapper-knockout neurons, RIM1 has a longer half-life with reduced ubiquitination, increased RIM1 levels, and elevated frequency of miniature excitatory postsynaptic currents. Co-immunoprecipitation, ubiquitination assay, Scrapper-KO mice, electrophysiology, RIM1 knockdown rescue experiment Cell High 17803915
2003 Rim1 interacts with Rab3A/B/C/D, Rab10, Rab26, and Rab37 in a GTP-dependent manner. Alternative splicing in the first alpha-helical region of the Rab-binding domain of Rim1 alters its Rab binding specificity. Cotransfection binding assay with 42 Rab proteins, site-directed mutagenesis, chimeric protein analysis The Journal of biological chemistry High 12578829
2003 RIM1 binds 14-3-3 proteins via phosphoserine residues (Ser-241 and Ser-287) located just C-terminal to the zinc finger; Ca2+/calmodulin-dependent protein kinase II phosphorylation greatly stimulates this interaction. Alkaline phosphatase treatment abolishes 14-3-3 binding. Yeast two-hybrid, in vitro protein binding, site-directed mutagenesis, CaMKII phosphorylation assay The Journal of biological chemistry High 12871946
2001 RIM1 is expressed in pancreatic beta-cells and localizes to the plasma membrane; transfection of the Rab3-binding domain of RIM1 into INS-1E cells enhances glucose-stimulated and Ca2+-stimulated insulin exocytosis, an effect reversed by co-expression of Rab3A. Northern blot, RT-PCR, Western blot, immunolocalization, transfection and exocytosis assay FEBS letters Medium 10828453
2001 The Rab3a-GTP binding domain of RIM1 consists of a ~30 amino acid sequence immediately N-terminal to the zinc finger, which is distinct from the zinc finger domain; the zinc finger domain alone enhances secretion independently of Rab3a binding and increases the rate of ATP-dependent priming without altering Ca2+ sensitivity. Deletion mutagenesis, Rab3a binding assays, permeabilized chromaffin cell exocytosis assay The Journal of biological chemistry High 11278839
2008 RIM1 gene encodes a second isoform RIM1beta (lacking the N-terminal Rab3-binding sequence of RIM1alpha) from a distinct promoter. RIM1alpha and RIM1beta together are required for mouse survival; double knockout shows abolished long-term presynaptic plasticity and severely impaired synaptic strength and short-term plasticity. Knockout mouse generation, electrophysiology, molecular cloning of RIM1beta The Journal of neuroscience High 19074017
2009 Domains of five active zone proteins converge on the N-terminal region of Munc13-1: the zinc-finger domain of RIM1 and the C-terminal region of Bassoon, a segment of CAST1/ELKS2, and coiled-coil domains of Aczonin/Piccolo. This interaction node is required for synaptic vesicle dynamics. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, expression of dominant-negative GFP fusions in neurons The Journal of neuroscience Medium 19812333
2005 In C. elegans, ELKS directly interacts with the PDZ domain of RIM (UNC-10) in vitro; however, RIM localizes independently of ELKS in vivo. RIM truncations containing only the PDZ and C2A domains target to release sites in an ELKS-dependent manner, indicating ELKS is one of multiple redundant anchors for RIM at active zones. Genetic analysis of C. elegans elks and rim mutants, yeast two-hybrid, behavioral and electrophysiological assays The Journal of neuroscience Medium 15976086
2006 In C. elegans, UNC-10/RIM localizes to dense projections at the presynaptic active zone and its loss causes an UNC-13-independent reduction in synaptic vesicles within 30 nm of dense projections, indicating RIM separately contributes to membrane localization of vesicles at the active zone. High-pressure freeze electron microscopy, immunogold staining, morphometric analysis in C. elegans mutants The Journal of neuroscience High 16885217
2013 Liprin-α2 recruits RIM1 to presynaptic sites and promotes its turnover there; depletion of liprin-α2 reduces RIM1 turnover at presynaptic terminals as measured by FRAP, and decreases synaptic vesicle pool size and synaptic output. Co-immunoprecipitation, FRAP (fluorescence recovery after photobleaching), KD/KO with electrophysiology and ultrastructure The Journal of cell biology High 23751498
2011 RIM1 physically associates with the Ca(V)beta auxiliary subunit and functionally regulates L-type Ca(V)1.2 and Ca(V)1.3 channels by decreasing the rate of current inactivation; knockdown of RIM1 in insulin-secreting cells increases inactivation and impairs glucose-stimulated insulin secretion. Co-immunoprecipitation, whole-cell patch clamp, siRNA knockdown, ELISA insulin secretion assay The Journal of biological chemistry High 21402706
2015 RIM1/2 conditional double knockout from rod photoreceptors causes a profound reduction in Ca2+ currents through Cav1.4 channels and nearly complete loss of evoked vesicle release, without altering Cav1.4 protein expression at ribbon synapses, indicating RIM1/2 facilitate Ca2+ channel opening (gating) rather than channel localization. Conditional knockout mice, whole-cell voltage-clamp recordings from rods, membrane capacitance measurements, immunofluorescence The Journal of neuroscience High 26400943
2017 Munc13 C2A domain heterodimerization with RIM is required for both optimal vesicle docking and priming; mutations that abolish C2A homodimerization or heterodimerization reveal that the Munc13-RIM heterodimer is an active component of the vesicle docking, priming and release complex, beyond being an inactivation-activation switch. Site-directed mutagenesis of C2A domain, electron microscopy (ultrastructure), electrophysiology in hippocampal cultures Nature communications High 28489077
2019 RIM1 (together with RIM2) is essential for dense-core vesicle (DCV) exocytosis in mammalian neurons; full-length RIM1 but not mutants lacking RAB3 or MUNC13 binding restores DCV release in RIM1/2-deficient neurons. A short N-terminal RIM1 fragment harboring only RAB3- and MUNC13-interacting domains is sufficient to support DCV exocytosis. Quadruple RAB3 knockout, RIM1/2 conditional knockout, live-cell imaging of DCV fusion events, domain rescue experiments Neuron High 31679900
2011 RIM1 reduces inhibitory G-protein regulation of Cav2.2 channels by promoting deinhibition (current recovery) following opioid receptor activation, through its interaction with the channel beta subunit, thereby sustaining Ca2+ influx during prolonged activity. Whole-cell patch clamp in HEK-293 cells, μ-opioid receptor activation, co-expression of RIM1 with Ca(V)2.2 Pflugers Archiv Medium 21331761
2014 RIM1 and RIM2 redundantly determine Ca2+ channel density and readily releasable pool size at the calyx of Held; single conditional KO of RIM1 has no effect while single KO of RIM2 causes a subtle reduction in Ca2+ current density, but double KO strongly reduces both presynaptic Ca2+ influx and RRP. Conditional knockout mice, direct presynaptic patch clamp at calyx of Held, RRP measurements Journal of neurophysiology High 25343783
2017 At mouse photoreceptor ribbon synapses, RIM1alpha and RIM1beta are absent and RIM2alpha is the major large RIM isoform; mouse photoreceptors express RIM2 variants lacking the Munc13 interaction domain, and loss of full-length RIM2alpha only marginally perturbs photoreceptor synaptic transmission, demonstrating a Munc13-independent priming mechanism at ribbon synapses. Immunofluorescence, Western blot, RIM2alpha mutant mouse analysis, ERG and synaptic transmission recordings The Journal of neuroscience High 28701482
2020 RIM modulates synaptic vesicle localization in the proximity of the active zone membrane independently of Munc13-1; both RIM and Munc13-1 are required together for vesicle docking and priming; RIM uniquely controls neurotransmitter release efficiency independent of Munc13-1. Genetic manipulations (KO/KD) of RIM and Munc13-1 in hippocampal neurons, electron microscopy ultrastructure, electrophysiology The Journal of neuroscience High 33139401
2007 The CORD7 disease-associated RIM1 arginine-to-histidine mutation (R844H in human; R655H in mouse) modifies RIM1's regulation of voltage-dependent Ca2+ channel currents elicited by P/Q-type Ca(v)2.1 and L-type Ca(v)1.4 channels. Electrophysiology in heterologous expression system, site-directed mutagenesis introducing the disease mutation Channels (Austin, Tex.) Medium 18690027
2003 RIM1 is expressed in photoreceptors of the retina where it localizes to presynaptic ribbons in ribbon synapses; the CORD7-associated G-to-A point mutation results in an Arg844His substitution in the C2A domain. cDNA cloning, immunolocalization, genomic analysis, mutation identification in CORD7 family Genomics Medium 12659814
2021 In C. elegans, UNC-10/RIM and SYD-2/Liprin-α regulate presynaptic localization of UNC-2 (CaV2) calcium channels; loss of UNC-10 greatly reduces UNC-2 channel puncta intensity and number at presynaptic terminals. Forward genetic screen, endogenous GFP tagging, quantitative fluorescence microscopy in live C. elegans, genetic epistasis in double/triple mutants The Journal of neuroscience High 33975919

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell 726 10412977
2001 Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron 324 11343654
1987 Peripherin. A rim-specific membrane protein of rod outer segment discs. Investigative ophthalmology & visual science 304 2433249
1997 The 220-kDa rim protein of retinal rod outer segments is a member of the ABC transporter superfamily. The Journal of biological chemistry 262 9092582
2001 A post-docking role for active zone protein Rim. Nature neuroscience 253 11559854
2001 U(L)31 and U(L)34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids. Journal of virology 249 11507225
2002 Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1. The Journal of cell biology 239 12163476
1996 Eps15 is a component of clathrin-coated pits and vesicles and is located at the rim of coated pits. The Journal of biological chemistry 221 8910509
1992 Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies. Neuron 206 1610568
2005 A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity? The EMBO journal 205 16052212
2000 The RIM/NIM family of neuronal C2 domain proteins. Interactions with Rab3 and a new class of Src homology 3 domain proteins. The Journal of biological chemistry 192 10748113
2002 A family of RIM-binding proteins regulated by alternative splicing: Implications for the genesis of synaptic active zones. Proceedings of the National Academy of Sciences of the United States of America 190 12391317
2005 The DEAD-box protein Dbp5p is required to dissociate Mex67p from exported mRNPs at the nuclear rim. Molecular cell 176 16307927
2007 SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell 172 17803915
2001 pH signaling in Sclerotinia sclerotiorum: identification of a pacC/RIM1 homolog. Applied and environmental microbiology 167 11133430
2003 Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2. The Journal of biological chemistry 159 12578829
2004 Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release. The Journal of cell biology 158 14734538
2001 Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. The Journal of biological chemistry 151 11438518
1997 The photoreceptor rim protein is an ABC transporter encoded by the gene for recessive Stargardt's disease (ABCR). FEBS letters 148 9202155
2003 Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins. The Journal of biological chemistry 146 12923177
2006 UNC-13 and UNC-10/rim localize synaptic vesicles to specific membrane domains. The Journal of neuroscience : the official journal of the Society for Neuroscience 128 16885217
2000 Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors. Radiology 128 11110952
2014 Bassoon specifically controls presynaptic P/Q-type Ca(2+) channels via RIM-binding protein. Neuron 127 24698275
2004 The novel yeast PAS kinase Rim 15 orchestrates G0-associated antioxidant defense mechanisms. Cell cycle (Georgetown, Tex.) 123 15300954
2001 A domain unique to plant RanGAP is responsible for its targeting to the plant nuclear rim. Proceedings of the National Academy of Sciences of the United States of America 104 11752475
2000 Astrocytes and blood vessels define the foveal rim during primate retinal development. Investigative ophthalmology & visual science 103 10967034
2006 Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch. PLoS biology 102 16732694
2013 Conserved arginines on the rim of Hfq catalyze base pair formation and exchange. Nucleic acids research 100 23771143
2013 Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission. The Journal of cell biology 92 23751498
1993 Molecular characterization of the yeast meiotic regulatory gene RIM1. Nucleic acids research 89 8367297
2006 Binding to Rab3A-interacting molecule RIM regulates the presynaptic recruitment of Munc13-1 and ubMunc13-2. The Journal of biological chemistry 84 16704978
2008 RIM1alpha and RIM1beta are synthesized from distinct promoters of the RIM1 gene to mediate differential but overlapping synaptic functions. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 19074017
2017 Heterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle docking and priming. Nature communications 77 28489077
2015 RIM-binding protein links synaptic homeostasis to the stabilization and replenishment of high release probability vesicles. Neuron 76 25704950
2009 A protein interaction node at the neurotransmitter release site: domains of Aczonin/Piccolo, Bassoon, CAST, and rim converge on the N-terminal domain of Munc13-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 76 19812333
2003 Genomic organisation and alternative splicing of human RIM1, a gene implicated in autosomal dominant cone-rod dystrophy (CORD7). Genomics 75 12659814
2016 RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses. Proceedings of the National Academy of Sciences of the United States of America 72 27671655
2015 The Cryptococcus neoformans alkaline response pathway: identification of a novel rim pathway activator. PLoS genetics 71 25859664
2008 RIM-BP3 is a manchette-associated protein essential for spermiogenesis. Development (Cambridge, England) 71 19091768
2009 Descemet membrane endothelial keratoplasty with a stromal rim (DMEK-S). The British journal of ophthalmology 70 19850580
2009 A model for DNA polymerase switching involving a single cleft and the rim of the sliding clamp. Proceedings of the National Academy of Sciences of the United States of America 68 19617571
2008 Macrocyclic nonviral vectors: high cell transfection efficiency and low toxicity in a lower rim guanidinium calix[4]arene. Organic letters 67 18722463
2007 Functional correlates of fundus autofluorescence abnormalities in patients with RPGR or RIMS1 mutations causing cone or cone rod dystrophy. The British journal of ophthalmology 67 17962389
1993 Hyperechoic renal tumors: anechoic rim and intratumoral cysts in US differentiation of renal cell carcinoma from angiomyolipoma. Radiology 66 8511293
2009 The NAC transcription factor RIM1 of rice is a new regulator of jasmonate signaling. The Plant journal : for cell and molecular biology 64 20015061
2005 RIM function in short- and long-term synaptic plasticity. Biochemical Society transactions 64 16246115
1997 Formation of the Drosophila ovarian ring canal inner rim depends on cheerio. Genetics 64 9093858
2004 Longitudinal health-related quality of life after mandibular resection for oral cancer: a comparison between rim and segment. Head & neck 63 14724907
2019 Differential Effects of Aging in the Macular Retinal Layers, Neuroretinal Rim, and Peripapillary Retinal Nerve Fiber Layer. Ophthalmology 60 31668716
2019 The RAB3-RIM Pathway Is Essential for the Release of Neuromodulators. Neuron 59 31679900
2000 The Rab3-interacting molecule RIM is expressed in pancreatic beta-cells and is implicated in insulin exocytosis. FEBS letters 59 10828453
2013 Spatial variations in microbial community composition in surface seawater from the ultra-oligotrophic center to rim of the South Pacific Gyre. PloS one 56 23405118
2005 Redundant localization mechanisms of RIM and ELKS in Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 56 15976086
2007 Interaction between Munc13-1 and RIM is critical for glucagon-like peptide-1 mediated rescue of exocytotic defects in Munc13-1 deficient pancreatic beta-cells. Diabetes 55 17639022
2004 Loss-of-function mutations at the rim of the funnel of mechanosensitive channel MscL. Biophysical journal 55 15041651
1992 Age-related decline of disc rim area in visually normal subjects. Ophthalmology 55 1741134
2006 The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates NFkappaB activation in Drosophila. Journal of cell science 53 17032737
2003 Rim, a component of the presynaptic active zone and modulator of exocytosis, binds 14-3-3 through its N terminus. The Journal of biological chemistry 52 12871946
2006 In situ SUMOylation analysis reveals a modulatory role of RanBP2 in the nuclear rim and PML bodies. Experimental cell research 51 16688858
2005 A detailed study of the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with mutation in the gene for RIM1. The British journal of ophthalmology 51 15665353
1993 Mandible preservation with oral cavity carcinoma: rim mandibulectomy versus sagittal mandibulectomy. American journal of surgery 47 8214304
2015 RIM1/2-Mediated Facilitation of Cav1.4 Channel Opening Is Required for Ca2+-Stimulated Release in Mouse Rod Photoreceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 26400943
2004 Cell lines that support replication of a novel herpes simplex virus 1 UL31 deletion mutant can properly target UL34 protein to the nuclear rim in the absence of UL31. Virology 42 15476875
2002 RIM1: an edge for presynaptic plasticity. Trends in neurosciences 42 12079752
1976 Sensory innervation in the rim of the octopus sucker. Journal of morphology 42 1003488
2017 A rim-and-spoke hypothesis to explain the biomechanical roles for cytoplasmic intermediate filament networks. Journal of cell science 40 29032358
2012 Physical and functional interaction between yeast Pif1 helicase and Rim1 single-stranded DNA binding protein. Nucleic acids research 39 23175612
2008 Experimental and computational studies of selective recognition of Hg2+ by amide linked lower rim 1,3-dibenzimidazole derivative of calix[4]arene: species characterization in solution and that in the isolated complex, including the delineation of the nanostructures. The Journal of organic chemistry 38 18590337
2007 Structure and evolution of RIM-BP genes: identification of a novel family member. Gene 38 17855024
2010 Functional analysis of the pH responsive pathway Pal/Rim in the phytopathogenic basidiomycete Ustilago maydis. Fungal genetics and biology : FG & B 37 20153837
2000 Autosomal dominant macular atrophy at 6q14 excludes CORD7 and MCDR1/PBCRA loci. Investigative ophthalmology & visual science 37 10634627
2018 The Rim Pathway Mediates Antifungal Tolerance in Candida albicans through Newly Identified Rim101 Transcriptional Targets, Including Hsp90 and Ipt1. Antimicrobial agents and chemotherapy 36 29311085
2012 Fife, a Drosophila Piccolo-RIM homolog, promotes active zone organization and neurotransmitter release. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 23197698
2020 Restriction of intramolecular motions (RIM) by metal-organic frameworks for electrochemiluminescence enhancement:2D Zr12-adb nanoplate as a novel ECL tag for the construction of biosensing platform. Biosensors & bioelectronics 35 32090871
2014 RIM1 and RIM2 redundantly determine Ca2+ channel density and readily releasable pool size at a large hindbrain synapse. Journal of neurophysiology 35 25343783
2021 Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim. F1000Research 34 33732436
2012 Lower rim guanidinocalix[4]arenes: macrocyclic nonviral vectors for cell transfection. Bioconjugate chemistry 34 22463059
2008 Retinal area and optic disc rim area in amblyopic, fellow, and normal hyperopic eyes: a hypothesis for decreased acuity in amblyopia. Ophthalmology 31 18801577
2011 Functional coupling of Rab3-interacting molecule 1 (RIM1) and L-type Ca2+ channels in insulin release. The Journal of biological chemistry 30 21402706
2001 Rab3a binding and secretion-enhancing domains in Rim1 are separate and unique. Studies in adrenal chromaffin cells. The Journal of biological chemistry 30 11278839
2023 Myeloid cell iron uptake pathways and paramagnetic rim formation in multiple sclerosis. Acta neuropathologica 29 37715818
2011 Speciation at the Mogollon Rim in the Arizona Mountain Kingsnake (Lampropeltis pyromelana). Molecular phylogenetics and evolution 29 21627995
2020 Disentangling the Roles of RIM and Munc13 in Synaptic Vesicle Localization and Neurotransmission. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 33139401
2013 Fluorescence and piezoresistive cantilever sensing of trinitrotoluene by an upper-rim tetrabenzimidazole conjugate of calix[4]arene and delineation of the features of the complex by molecular dynamics. ACS applied materials & interfaces 27 24320549
2021 Risk Score for Predicting In-Hospital Mortality in COVID-19 (RIM Score). Diagnostics (Basel, Switzerland) 26 33810534
2017 Analysis of RIM Expression and Function at Mouse Photoreceptor Ribbon Synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 28701482
1997 Structure of the herpes simplex virus capsid: peptide A862-H880 of the major capsid protein is displayed on the rim of the capsomer protrusions. Virology 26 9123829
2021 UNC-2 CaV2 Channel Localization at Presynaptic Active Zones Depends on UNC-10/RIM and SYD-2/Liprin-α in Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 33975919
2015 A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones. eLife 25 26274777
2014 Free energy landscape of rim-pore expansion in membrane fusion. Biophysical journal 24 25418297
2009 Spectroscopy and microscopy studies of the recognition of amino acids and aggregation of proteins by Zn(II) complex of lower rim naphthylidene conjugate of calix[4]arene. The journal of physical chemistry. B 24 19678658
2007 Mutation associated with an autosomal dominant cone-rod dystrophy CORD7 modifies RIM1-mediated modulation of voltage-dependent Ca2+ channels. Channels (Austin, Tex.) 24 18690027
2007 Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation. Journal of medical genetics 23 17237123
1997 Rim enhancement in colorectal metastases at CT during infusion hepatic arteriography. Does it represent liver parenchyma or live tumor cell zone? Acta radiologica (Stockholm, Sweden : 1987) 23 9191433
2009 Rab3a interacting molecule (RIM) and the tethering of pre-synaptic transmitter release site-associated CaV2.2 calcium channels. Journal of neurochemistry 22 19878533
1985 Evaluation of the RIM-N, Gonochek II, and Phadebact systems for the identification of pathogenic Neisseria spp. and Branhamella catarrhalis. Journal of clinical microbiology 22 3889044
2017 Efficient stimulus-secretion coupling at ribbon synapses requires RIM-binding protein tethering of L-type Ca2+ channels. Proceedings of the National Academy of Sciences of the United States of America 21 28874522
2016 Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism. Blood 21 28011674
2011 Rim1 modulates direct G-protein regulation of Ca(v)2.2 channels. Pflugers Archiv : European journal of physiology 21 21331761
2014 The arterial blood supply of the helical rim and the earlobe-based advancement flap (ELBAF): a new strategy for reconstructions of helical rim defects. Journal of plastic, reconstructive & aesthetic surgery : JPRAS 20 25260854