Affinage

GJD2

Gap junction delta-2 protein · UniProt Q9UKL4

Length
321 aa
Mass
36.1 kDa
Annotated
2026-06-10
61 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GJD2 encodes connexin-36 (Cx36), the principal gap junction protein of mammalian neurons and pancreatic beta-cells, where it assembles into intercellular channels that mediate electrical and small-molecule coupling (PMID:9753189, PMID:12064610, PMID:10905480). Cloned as a 321-residue connexin expressed predominantly in CNS neurons (inferior olive, olfactory bulb, hippocampus, retina), Cx36 is restricted to neuronal gap junctions—including 'mixed' glutamatergic/electrical synapses—and is segregated from the astrocytic and oligodendroglial connexins, defining a dedicated neuronal electrical-coupling pathway (PMID:9753189, PMID:12064610, PMID:16841170). Cryo-EM of the human channel shows that inhibitors (mefloquine, arachidonic acid, 1-hexanol) compete for a pocket at the N-terminal helices, shifting them from a pore-lining to a flexible state that obstructs the pore, while mefloquine blocks Cx36 channels with nanomolar selectivity (PMID:39455592, PMID:15297615); in the hemichannel configuration the pore selectively permeates ATP but excludes glutamate and lactate, a selectivity set by N-terminal charge [PMID:bio_10.1101_2025.03.12.642803], and functional E2-loop electrostatic pairs govern docking and homotypic specificity [PMID:bio_10.1101_2025.10.25.684567]. Channel activity is tuned by C-terminal regulatory inputs: Ca2+-loaded calmodulin binds the C-terminus in a compact mode anchored at W277/V284 to activate the channel (PMID:27917108), and a glutamate→Ca2+→CaMKII pathway potentiates coupling (PMID:32179580), with CaMKII phosphorylation weakening the channel's ZO-1 PDZ interaction as part of synaptic potentiation [PMID:bio_10.1101_2025.10.27.684941]. Trafficking is directed by the C-terminal tip, where a terminal valine recruits COPII Sec24 for ER export and the 'SAYV' PDZ motif binds Grasp55 for Golgi retention (PMID:39395036), and the electrical-synapse scaffold includes ZO-1/ZO-2 and Sipa1l3 [PMID:bio_10.1101_2024.11.26.625481]. In islets, Cx36 coupling synchronizes beta-cell Ca2+ oscillations, hyperpolarizes inactive neighbors, confines the glucose-stimulated range, and controls insulin secretion upstream of KATP-channel membrane-potential control (PMID:17395748, PMID:24458355, PMID:14681053), and a human GJD2 variant that impairs coupling reduces islet Cx36 and beta-cell survival to cause hyperglycemia (PMID:26959991).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing the molecular identity of the first predominantly neuronal connexin defined a dedicated electrical-coupling pathway in the CNS.

    Evidence Degenerate RT-PCR cloning, in situ hybridization, and neurotoxin lesions across rodent brain regions

    PMID:9753189

    Open questions at the time
    • Cloning alone did not define channel gating or partners
    • Functional electrical coupling not yet demonstrated
  2. 2001 High

    Ultrastructural localization resolved whether neuronal and glial gap junctions use the same connexin, showing Cx36 is exclusive to neuronal gap junctions.

    Evidence Freeze-fracture replica immunogold labeling (FRIL) across thousands of gap junctions in adult rat CNS

    PMID:12064610

    Open questions at the time
    • Did not address channel conductance or regulation
    • Did not identify scaffolding partners
  3. 2000 High

    Identifying Cx36 expression in pancreatic beta-cells extended its role beyond neurons to endocrine electrical coupling.

    Evidence In situ hybridization, immunolabeling, and FACS-purified beta/non-beta cell preparations

    PMID:10905480

    Open questions at the time
    • Functional consequence for insulin secretion not yet established
  4. 2007 High

    Defining how beta-cell coupling shapes secretion showed Cx36 hyperpolarizes inactive neighbors and reduces cellular heterogeneity, acting upstream of KATP-controlled membrane potential.

    Evidence Electrophysiology and Ca2+ imaging in islets of Cx36 knockout vs wild-type mice, secretion assays, and genetic epistasis with ATP-insensitive KATP channels

    PMID:14681053 PMID:15023528 PMID:17395748 PMID:24458355

    Open questions at the time
    • Molecular determinants of beta-cell channel gating not addressed here
    • Human translation initially inferred from rodent models
  5. 2008 High

    Human islet studies confirmed Cx36 channels mediate cation-selective coupling clustered in lipid rafts and that expression tracks insulin gene levels.

    Evidence Immunolabeling, lipid raft fractionation, tracer coupling, and RT-PCR in control and type 2 diabetic human islets

    PMID:19000992

    Open questions at the time
    • Causality between Cx36 loss and diabetes not directly tested in humans
  6. 2002 Medium

    Mapping trafficking determinants identified the N-terminal domain as required for plaque localization and excluded phosphorylation as the major transport switch.

    Evidence Cx36-EGFP mutagenesis, confocal imaging, and electrophysiology in neuroblastoma cells

    PMID:12210839

    Open questions at the time
    • Specific export/retention signals not yet defined
    • No interacting trafficking machinery identified
  7. 2004 High

    Pharmacological identification of mefloquine as a selective Cx36 blocker provided a tool to dissect electrical synapse function.

    Evidence Electrophysiology in transfected N2A cells and acute neocortical slices

    PMID:15297615

    Open questions at the time
    • Binding site not resolved at the time
    • Mechanism of block undefined until cryo-EM
  8. 2016 High

    Solving how Ca2+ signaling regulates the channel showed Ca2+-CaM binds the Cx36 C-terminus in a compact mode at W277/V284 to activate, an inverse of other connexins.

    Evidence NMR solution structure with Co-IP, electrophysiology, and calcium-dependence assays

    PMID:27917108

    Open questions at the time
    • In vivo relevance of CaM activation at native synapses not shown
    • Interplay with CaMKII at the overlapping site not fully resolved
  9. 2020 Medium

    Establishing a glutamate→Ca2+→CaMKII→Cx36 axis defined how excitatory signaling potentiates electrical synapses.

    Evidence Cx36-GCaMP biosensor, tracer coupling, and pharmacological CaMKII inhibition in mammalian cells with retinal phospho-state correlations

    PMID:26483638 PMID:29311815 PMID:32179580

    Open questions at the time
    • Direct kinase-Cx36 phosphorylation effect not validated in all systems
    • Phospho-Ser293 data is single antibody-based and correlative
  10. 2018 Medium

    Identifying cysteine residues forming an anesthetic/alcohol pocket explained how short-chain n-alcohols and isoflurane modulate Cx36 conductance.

    Evidence Cysteine substitution mutagenesis, structural modeling, and dual whole-cell patch-clamp in HeLa and N2A cells

    PMID:29298877

    Open questions at the time
    • Proposed disulfide re-shuffling not directly observed structurally
    • Single lab
  11. 2024 High

    Cryo-EM of the human channel with multiple inhibitors revealed a shared N-terminal-helix pocket whose occupancy converts the pore-lining state to a flexible, pore-obstructing conformation.

    Evidence Cryo-electron microscopy of human Cx36 gap junction channels bound to mefloquine, arachidonic acid, and 1-hexanol

    PMID:39455592

    Open questions at the time
    • Structures of activated/CaM-bound states not captured
    • Physiological lipid regulation not directly tested
  12. 2024 High

    Defining C-terminal tip interactions explained how Cx36 traffics, with a terminal valine recruiting COPII Sec24 for ER export and the SAYV PDZ motif binding Grasp55 for Golgi retention.

    Evidence siRNA screens, BioID, Co-IP, and confocal ER-retention phenotyping in HEK293T cells

    PMID:39395036

    Open questions at the time
    • Regulation of the export/retention balance in neurons not shown
    • How trafficking couples to synapse assembly unclear
  13. 2025 Medium

    Defining the electrical-synapse proteome and the tunable ZO-1 interaction explained scaffold organization and a potentiation switch in which CaMKII phosphorylation weakens ZO-1 binding.

    Evidence In vivo BioID in mouse AII amacrine cells and zebrafish (preprint), Co-IP, and Gaussian accelerated molecular dynamics with binding/phosphorylation assays (preprint)

    PMID:bio_10.1101_2024.11.26.625481 PMID:bio_10.1101_2025.10.27.684941

    Open questions at the time
    • Preprints not yet peer-reviewed
    • Functional consequences of Sipa1l3 and most new interactors untested in vivo
  14. 2025 Medium

    Permselectivity and docking studies showed Cx36 hemichannels release ATP but not glutamate/lactate (set by N-terminal charge) and require multiple E2 electrostatic pairs for functional, homotypic-specific docking.

    Evidence Genetically encoded sensor assays and N-terminal mutagenesis (preprint); E2-loop mutagenesis with electrostatic calculations and dual patch-clamp in HEK293 pairs (preprint)

    PMID:bio_10.1101_2025.03.12.642803 PMID:bio_10.1101_2025.10.25.684567

    Open questions at the time
    • Preprints not yet peer-reviewed
    • Physiological role of hemichannel ATP release in vivo not established
  15. 2025 High

    Cell-type-specific knockout clarified that islet Ca2+ coordination combines paracrine signaling with low-density Cx36 coupling, refining the role of gap junctions across endocrine cell types.

    Evidence Delta-cell-specific Cx36 knockout, GCaMP6s imaging of beta and delta cell populations, and vesicle-release blockade

    PMID:40956879

    Open questions at the time
    • Relative weighting of paracrine vs electrical coupling under physiological glucose ranges not fully quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the C-terminal regulatory inputs (CaM, CaMKII, ZO-1 unbinding) are integrated with the cryo-EM gating conformations to produce activity-dependent plasticity in vivo remains unresolved.
  • No structure of the CaM- or CaMKII-regulated activated channel
  • Causal in vivo link between phospho-state, ZO-1 unbinding, and synaptic potentiation not established
  • Human disease causality of GJD2 variants beyond a single engineered SNP not broadly demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0005198 structural molecule activity 3 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-9609507 Protein localization 1
Partners
CALM1CAMK2BCAMK2DGORASP2SEC24ASIPA1L3TJP1TJP2
Complex memberships
Cx36 gap junction channelelectrical synapse

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Cx36 (GJD2) was cloned as a new gap junction protein of 321 amino acids, predominantly expressed in mammalian neurons (inferior olive, olfactory bulb, hippocampal CA3/CA4, brainstem nuclei, retina), making it the first connexin shown to be expressed predominantly in neuronal cells of the mammalian CNS. Degenerate RT-PCR cloning, genomic library isolation, in situ hybridization, neurotoxin lesion experiments confirming neuronal localization The European journal of neuroscience High 9753189
2001 Using freeze-fracture replica immunogold labeling (FRIL), Cx36 was exclusively localized to neuronal gap junctions in adult rat CNS, while Cx26/Cx30/Cx43 were confined to astrocyte gap junctions and Cx32 to oligodendrocytes, establishing separate gap-junctional communication pathways for neurons vs. glia. Freeze-fracture replica immunogold labeling (FRIL) and confocal immunocytochemistry Cell communication & adhesion High 12064610
2000 Cx36 is expressed in pancreatic islet beta-cells, concentrated in centrally located insulin-producing cells, with much lower or absent expression in non-beta endocrine cells, establishing selective gap junctional communication pathways within islets. In situ hybridization, immunolabeling with affinity-purified antibodies, FACS-purified beta/non-beta cell preparations Diabetes High 10905480
2003 Cx36-dependent gap junctions modulate insulin secretion by controlling cytosolic Ca2+ handling in populations of insulin-producing cells; loss of Cx36 expression in MIN6 cells abolished glucose-stimulated insulin secretion and altered Ca2+ dynamics. Antisense Cx36 stable transfection, insulin secretion assays, cytosolic Ca2+ monitoring Cell communication & adhesion Medium 14681053
2004 Mefloquine potently and selectively blocks Cx36 gap junction channels (IC50 ~300 nM) expressed in N2A neuroblastoma cells, and blocks gap junctional coupling between neocortical interneurons in brain slices at 25 µM with minimal effects on excitatory/inhibitory postsynaptic potentials or intrinsic cellular properties. Electrophysiology in transfected N2A cells and acute neocortical brain slices, pharmacological channel block Proceedings of the National Academy of Sciences of the United States of America High 15297615
2004 Restoration of Cx36 (but not E-cadherin) expression in Cx36 antisense-transfected MIN6 cells recovered normal insulin secretion in response to various secretagogues, demonstrating that Cx36 gap junction channels specifically control steps of beta-cell secretion independent of E-cadherin. Lentivirus-mediated transduction of Cx36 or E-cadherin into Cx36 antisense MIN6 clones, insulin secretion assays Experimental cell research Medium 15023528
2007 Cx36-mediated electrical coupling between beta-cells hyperpolarizes adjacent inactive cells; in Cx36 knockout mice, beta-cells with blocked KATP channels rapidly depolarized and exhibited continuous electrical activity, demonstrating that Cx36 coupling reduces beta-cell heterogeneity, confines the stimulating glucose concentration range, and affects insulin release kinetics. Electrophysiological recordings from beta-cells in acute pancreatic slices of Cx36+/+, Cx36+/-, and Cx36-/- mice Diabetes High 17395748
2008 Human beta-cells harbor Cx36-containing gap junctions concentrated in lipid raft membrane domains; Cx36 channels preferentially allow exchange of cationic molecules between human beta-cells, and Cx36 mRNA levels correlate with insulin gene expression in control and type 2 diabetic islets. Immunolabeling of human islets, lipid raft fractionation, functional coupling assays with cationic/anionic tracer molecules, RT-PCR Human molecular genetics High 19000992
2002 The N-terminal domain of Cx36 contains a structural element required for normal subcellular localization; N-terminal mutagenesis disrupted localization to gap junction plaques, whereas mutagenesis of putative phosphorylation motifs did not alter localization, excluding phosphorylation/dephosphorylation as a major regulatory step in Cx36 protein transport. Cx36-EGFP transfection in neuroblastoma cells, site-directed mutagenesis, confocal imaging, electrophysiology Journal of neuroscience research Medium 12210839
2012 Beta2/NeuroD1 transcription factor binds to three E boxes in a 2-kbp fragment of the Gjd2 (Cx36) promoter and, together with cofactor E47, transactivates the Gjd2 promoter, establishing Beta2/NeuroD1 as a transcriptional regulator of Cx36 expression during beta-cell differentiation. Promoter-reporter assays, chromatin immunoprecipitation / electrophoretic mobility shift assay (E-box binding), developmental expression analysis in mouse pancreas The Journal of membrane biology Medium 22729650
2016 Ca2+-loaded calmodulin (CaM) binds to the C-terminus of Cx36 in a calcium-dependent manner at an overlapping site with CaMKII; NMR solution structure shows CaM binds Cx36 in a compact state with key hydrophobic contacts at W277 (anchor position 1) and V284 (position 8); Ca2+-CaM binding activates Cx36 channels, a mechanism distinct from other connexins. NMR spectroscopy (solution structure), co-immunoprecipitation, electrophysiology, calcium-dependence assays Frontiers in molecular neuroscience High 27917108
2017 CaMKII-β and CaMKII-δ colocalize specifically with Cx36-containing gap junctions in the mouse retina: CaMKII-β colocalizes with Cx36 in both the inner and outer retina, while CaMKII-δ is confined to Cx36 puncta in the inner retina (bipolar and AII amacrine cells), indicating isoform-specific regulation of Cx36 gap junctions. Confocal immunofluorescence double-labeling for Cx36 and four CaMKII isoforms in mouse retina Frontiers in molecular neuroscience Medium 29311815
2014 Genetic knockout of Cx36 in mice expressing ATP-insensitive KATP channels rescued glucose homeostasis: islets lacking Cx36 showed near-normal glucose-stimulated Ca2+ activity and insulin secretion, demonstrating that Cx36 gap junction coupling coordinates beta-cell electrical activity upstream of KATP channel-mediated membrane potential control. Genetic epistasis (Cx36 KO crossed with ATP-insensitive KATP channel transgenic mice), glucose homeostasis measurements, islet Ca2+ imaging, insulin secretion assays Diabetes High 24458355
2018 Cysteine residues C264 (TM4), C92, and C87 (TM2) of Cx36 form a unique binding pocket accessible to short-chain n-alcohols and isoflurane; mutagenesis of these cysteines reversed the stimulatory effect of hexanol and isoflurane on Cx36 GJ conductance to inhibitory, suggesting that re-shuffling of inter-subunit disulfide bonds (C264–C92) to intra-subunit bonds (C264–C87) underlies the stimulatory mechanism. Structural modeling/docking, cysteine substitution mutagenesis, dual whole-cell patch-clamp in HeLa and N2A cells Bioscience reports Medium 29298877
2015 Phosphorylation of Cx36 at Ser293 is significantly increased in AII amacrine cells of rd10 and rd1 retinal degeneration mouse models compared to wild-type, suggesting elevated Cx36 phosphorylation state underlies increased gap junction coupling associated with aberrant activity in degenerating retina. Immunolabeling with phospho-Ser293 Cx36-specific antibody in rd10 and rd1 vs. wild-type mouse retinas Frontiers in cellular neuroscience Low 26483638
2024 Cryo-EM structures of human Cx36 gap junction channels in complex with mefloquine, arachidonic acid, and 1-hexanol reveal that all three inhibitors competitively bind a pocket at the N-terminal helices (NTH), inducing a conformational shift from the pore-lining NTH (PLN) state to a flexible NTH (FN) state, causing channel pore obstruction by lipid bilayer double-layer densities. Cryo-electron microscopy structural determination of human Cx36 GJC with bound inhibitors Nature communications High 39455592
2024 The C-terminal tip of Cx36 mediates two distinct protein interactions in the early secretory pathway: the terminal valine serves as an ER export signal recruiting COPII cargo receptors Sec24A/B/C at ER exit sites, while the PDZ binding motif 'SAYV' mediates interaction with Golgi stacking protein Grasp55, which stabilizes Cx36 in the Golgi; these interactions have opposing effects (Sec24 exports from ER, Grasp55 retains in Golgi). siRNA knockdown screens, BioID proximity labeling, co-immunoprecipitation, overexpression in HEK293T cells, confocal microscopy of ER retention phenotypes Cellular and molecular life sciences : CMLS High 39395036
2024 In vivo BioID proximity labeling in mouse AII amacrine cells and zebrafish retinal neurons identified the electrical synapse proteome of Cx36/Cx35b, including known interactors ZO-1 and ZO-2 and >50 new proteins including scaffold proteins, adhesion molecules, and cytoskeletal regulators; Sipa1l3 was identified as a new Cx36 scaffold protein that interacts with ZO-1, ZO-2, and Cx36. In vivo BioID proximity labeling (GFP-nanobody-TurboID in mouse AII amacrine cells; Cx35b-TurboID transgenic zebrafish), mass spectrometry, co-immunoprecipitation validation bioRxivpreprint Medium bio_10.1101_2024.11.26.625481
2025 Molecular dynamics simulations combined with binding assays identified that: (1) a single substitution at position 319 in the PDZ binding motif of Cx36 massively increases ZO-1 PDZ1 binding; (2) acidic residues adjacent to the PDZ binding motif are evolutionarily tuned to weaken PDZ interactions; (3) CaMKII-mediated phosphorylation of Cx36 reduces ZO-1 PDZ1 binding, suggesting ZO-1 unbinding is a necessary step for potentiation of electrical synapses. Gaussian accelerated molecular dynamics simulations, mutagenesis, binding assays, phosphorylation assays bioRxivpreprint Medium bio_10.1101_2025.10.27.684941
2025 Systematic mutagenesis of key charged residues in the second extracellular (E2) loop of Cx36, guided by cryo-EM-defined electrostatic interaction pairs, showed that at least three electrostatic interaction pairs per E2-E2 interface are required for functional gap junction formation; these unique electrostatic interactions also contribute to Cx36 docking specificity (rarely forming heterotypic GJs with other brain connexins). Mutagenesis of E2 interface residues, computational electrostatic calculations, dual whole-cell patch-clamp in HEK293 cell pairs bioRxivpreprint Medium bio_10.1101_2025.10.25.684567
2020 A Cx36-GCaMP fusion protein forms functional gap junctions that support tracer coupling regulated by PKA signaling, and reports local Ca2+ increases at gap junctions; glutamate receptor activation (via endogenous NMDA and kainate receptors in HeLa cells) potentiated Cx36 tracer coupling through a mechanism dependent on CaMKII activity, establishing a glutamate→Ca2+→CaMKII→Cx36 potentiation pathway at electrical synapses. Cx36-GCaMP biosensor in transfected mammalian cells, Ca2+ imaging, Neurobiotin tracer coupling assays, pharmacological CaMKII inhibition, RNA-seq confirmation of NMDA receptor subunit expression eNeuro Medium 32179580
2008 Loss-of-function mutation in zebrafish cx36.7/ecx (an early cardiac connexin) caused disorganization of myofibrils and heart malformation due to downregulation of nkx2.5 expression; rescue experiments showed Nkx2.5 is a downstream mediator of Ecx-mediated signaling, placing Cx36.7 upstream of nkx2.5 in cardiac morphogenesis. Zebrafish ftk mutant analysis, in situ hybridization, rescue experiment with nkx2.5 Proceedings of the National Academy of Sciences of the United States of America Medium 18337497
2021 Depletion of gjd2a (Cx35.5) in zebrafish caused hyperopia and electrophysiological changes in the retina, while depletion of gjd2b (Cx35.1) caused nuclear cataract triggering axial elongation, providing functional evidence that GJD2 orthologs regulate ocular biometry and refractive error development. Zebrafish gjd2a/gjd2b morpholino/CRISPR depletion, ocular biometry, electroretinography, immunohistochemistry, scRNA sequencing Communications biology Medium 34083742
2016 A synonymous SNP of human GJD2 (rs3743123) expressed in connexin-lacking HeLa cells resulted in altered formation of gap junction plaques and reduced cell coupling compared to wild-type; transgenic mice expressing this variant under insulin promoter showed post-natal reduction of islet Cx36 levels and beta-cell survival, causing hyperglycemia. HeLa cell transfection with WT vs. SNP cDNA, gap junction plaque quantification, cell coupling assay; transgenic mouse lines with insulin promoter-driven expression PloS one Medium 26959991
2006 Using FRIL ultrastructural immunogold labeling, Cx36 (and less abundantly Cx45) were localized to neuronal gap junctions at 'mixed' glutamatergic/electrical synapses between presumptive mitral/tufted cell dendrites in the olfactory bulb, while Cx36 was absent from olfactory receptor neuron axons which had no gap junctions. Freeze-fracture replica immunogold labeling (FRIL), confocal immunofluorescence microscopy Journal of neurocytology High 16841170
2025 Cx36 hemichannels selectively allow release of ATP but not glutamate or lactate, demonstrating that the size of the permeating molecule is not the sole determinant of Cx36 hemichannel permselectivity; mutational analysis of the closely related Cx46/Cx50 hemichannels identified the N-terminus charge and N-terminus-TM2 interactions as key contributors to permselectivity for ATP. Co-expression of genetically encoded fluorescent sensors (for ATP, glutamate, lactate) with connexins in cells, pharmacological stimulation, mutagenesis of N-terminus residues bioRxivpreprint Medium bio_10.1101_2025.03.12.642803
2025 Selective knockout of Cx36 in delta cells confirmed that gap junctions contribute to coordination of delta cell Ca2+ oscillations with beta cells; however, blockade of vesicle release completely removed coupling between beta and most delta cells, demonstrating that coordination is mediated by a combination of paracrine signaling and low-density Cx36 gap junction coupling. Cell-type-specific Cx36 knockout, GCaMP6s Ca2+ imaging of hundreds of beta and delta cells simultaneously, ML-141 vesicle release blockade Proceedings of the National Academy of Sciences of the United States of America High 40956879

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons. The European journal of neuroscience 377 9753189
2004 Potent block of Cx36 and Cx50 gap junction channels by mefloquine. Proceedings of the National Academy of Sciences of the United States of America 272 15297615
2000 Expression of Cx36 in mammalian neurons. Brain research. Brain research reviews 220 10751658
2001 Identification of cells expressing Cx43, Cx30, Cx26, Cx32 and Cx36 in gap junctions of rat brain and spinal cord. Cell communication & adhesion 180 12064610
2007 Cx36-mediated coupling reduces beta-cell heterogeneity, confines the stimulating glucose concentration range, and affects insulin release kinetics. Diabetes 141 17395748
2000 Cx36 preferentially connects beta-cells within pancreatic islets. Diabetes 138 10905480
2001 Global ischemia-induced increases in the gap junctional proteins connexin 32 (Cx32) and Cx36 in hippocampus and enhanced vulnerability of Cx32 knock-out mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 119 11567043
2008 Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression. Human molecular genetics 100 19000992
1999 Structure, chromosomal localization, and brain expression of human Cx36 gene. Journal of neuroscience research 90 10462698
2006 Ultrastructural localization of connexins (Cx36, Cx43, Cx45), glutamate receptors and aquaporin-4 in rodent olfactory mucosa, olfactory nerve and olfactory bulb. Journal of neurocytology 76 16841170
2012 Impaired β-cell-β-cell coupling mediated by Cx36 gap junctions in prediabetic mice. American journal of physiology. Endocrinology and metabolism 62 22569071
2000 Cx36 is dynamically expressed during early development of mouse brain and nervous system. Neuroreport 46 11117498
2004 Differentiating the effects of Cx36 and E-cadherin for proper insulin secretion of MIN6 cells. Experimental cell research 42 15023528
2002 Evidence for a role of the N-terminal domain in subcellular localization of the neuronal connexin36 (Cx36). Journal of neuroscience research 42 12210839
2021 Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish. Communications biology 27 34083742
2017 Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36). Frontiers in molecular neuroscience 27 29311815
2008 Zebrafish early cardiac connexin, Cx36.7/Ecx, regulates myofibril orientation and heart morphogenesis by establishing Nkx2.5 expression. Proceedings of the National Academy of Sciences of the United States of America 27 18337497
2016 Structural and Functional Consequences of Connexin 36 (Cx36) Interaction with Calmodulin. Frontiers in molecular neuroscience 25 27917108
2010 Visual responses in the lateral geniculate evoked by Cx36-independent rod pathways. Vision research 21 20709095
2014 Decreasing cx36 gap junction coupling compensates for overactive KATP channels to restore insulin secretion and prevent hyperglycemia in a mouse model of neonatal diabetes. Diabetes 20 24458355
2012 Connexin36 (Cx36) expression and protein detection in the mouse carotid body and myenteric plexus. Acta histochemica 18 22897942
2019 Rod Photoreceptors Signal Fast Changes in Daylight Levels Using a Cx36-Independent Retinal Pathway in Mouse. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 31776212
2017 Cx36, Cx43 and Cx45 in mouse and rat cerebellar cortex: species-specific expression, compensation in Cx36 null mice and co-localization in neurons vs. glia. The European journal of neuroscience 17 28561933
2016 A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells. PloS one 17 26959991
2015 Increased phosphorylation of Cx36 gap junctions in the AII amacrine cells of RD retina. Frontiers in cellular neuroscience 17 26483638
2003 Cx36 involvement in insulin secretion: characteristics and mechanism. Cell communication & adhesion 17 14681053
2001 Cx36 and the function of endocrine pancreas. Cell communication & adhesion 17 12064624
2018 Neuroprotective effects of leonurine against oxygen-glucose deprivation by targeting Cx36/CaMKII in PC12 cells. PloS one 15 30016355
2012 The intercellular synchronization of Ca2+ oscillations evaluates Cx36-dependent coupling. PloS one 15 22848521
2013 Evaluating the association between pathological myopia and SNPs in RASGRF1. ACTC1 and GJD2 genes at chromosome 15q14 and 15q25 in a Chinese population. Ophthalmic genetics 14 23834555
2022 The Role of GJD2(Cx36) in Refractive Error Development. Investigative ophthalmology & visual science 13 35262731
2018 Cx36 in the mouse hippocampus during and after pilocarpine-induced status epilepticus. Epilepsy research 13 29476948
2021 Phenotypic Consequences of the GJD2 Risk Genotype in Myopia Development. Investigative ophthalmology & visual science 12 34406332
2019 Decreased expression of gap junction delta-2 (GJD2) messenger RNA and connexin 36 protein in form-deprivation myopia of guinea pigs. Chinese medical journal 12 31283648
2012 Cx36 is a target of Beta2/NeuroD1, which associates with prenatal differentiation of insulin-producing β cells. The Journal of membrane biology 12 22729650
2010 Role of Cx36 gap junction modulation in general anaesthetic anticonvulsant action. European journal of pharmacology 12 20599911
2016 The role of Cx36 and Cx43 in 4-aminopyridine-induced rhythmic activity in the spinal nociceptive dorsal horn: an electrophysiological study in vitro. Physiological reports 11 27462070
2020 Localized Calcium Signaling and the Control of Coupling at Cx36 Gap Junctions. eNeuro 10 32179580
2002 Mutational analysis of the connexin 36 gene (CX36) and exclusion of the coding sequence as a candidate region for catatonic schizophrenia in a large pedigree. Schizophrenia research 10 12363395
2017 The inhibitor of connexin Cx36 channels, mefloquine, inhibits voltage-dependent Ca2+ channels and insulin secretion. Molecular and cellular endocrinology 9 29208420
2021 The Roles of Calmodulin and CaMKII in Cx36 Plasticity. International journal of molecular sciences 8 33922931
2021 The Role of Retinal Connexins Cx36 and Horizontal Cell Coupling in Emmetropization in Guinea Pigs. Investigative ophthalmology & visual science 8 34283211
2021 Extensive GJD2 Expression in the Song Motor Pathway Reveals the Extent of Electrical Synapses in the Songbird Brain. Biology 6 34827092
2018 Molecular basis for potentiation of Cx36 gap junction channel conductance by n-alcohols and general anesthetics. Bioscience reports 6 29298877
2017 Dynamic Expression of CX36 Protein in Kainic Acid Kindling induced Epilepsy. Translational neuroscience 6 28729916
2022 Astragaloside IV ameliorates cerebral ischemia-reperfusion injury via upregulation of PKA and Cx36. Neuroreport 5 36126263
2025 Heterogeneity in the coordination of delta cells with beta cells is driven by both paracrine signals and low-density Cx36 gap junctions. Proceedings of the National Academy of Sciences of the United States of America 4 40956879
2020 Cadmium versus Lanthanum Effects on Spontaneous Electrical Activity and Expression of Connexin Isoforms Cx26, Cx36, and Cx45 in the Human Fetal Cortex. Cerebral cortex (New York, N.Y. : 1991) 4 31408166
2020 Altered Expression of GJD2 Messenger RNA and the Coded Protein Connexin 36 in Negative Lens-induced Myopia of Guinea Pigs. Optometry and vision science : official publication of the American Academy of Optometry 4 33278187
2019 Gap junctions and expression of Cx36, Cx43 and Cx45 in the posterodorsal medial amygdala of adult rats. Histology and histopathology 3 31495909
2015 Cx36 expression in the AII-mediated rod pathway is activity dependent in the developing rabbit retina. Developmental neurobiology 3 26084632
2024 Trafficking of Connexin36 (Cx36) in the early secretory pathway. bioRxiv : the preprint server for biology 2 38585986
2024 Characterizing ER Retention Defects of PDZ Binding Deficient Cx36 Mutants Using Confocal Microscopy. Bio-protocol 2 39100594
2024 Regulation of Cx36 trafficking through the early secretory pathway by COPII cargo receptors and Grasp55. Cellular and molecular life sciences : CMLS 2 39395036
2024 Mefloquine-induced conformational shift in Cx36 N-terminal helix leading to channel closure mediated by lipid bilayer. Nature communications 2 39455592
2022 Early decrease in Cx36 is associated with increased cell adhesion molecules (CAMs) junctional content in mouse pancreatic islets after short-term high-fat diet feeding. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 2 35114378
2025 (-) - (11R, 12S)-mefloquine ameliorates neuropathic pain by modulating Cx36-ER stress interaction in the pain-related central nervous system in rats. Life sciences 1 39828229
2022 Association of CX36 Protein Encoding Gene GJD2 with Refractive Errors. Genes 1 35885949
2025 Whole exome sequencing identified mutations of forkhead box I 1 (FOXI1), keratin 6 C (KRT6C) and gap junction protein delta 2 (GJD2) in a low-grade oncocytic tumor of the kidney: a case report. Diagnostic pathology 0 39980061
2025 Retinal Cx36 gap junctions in the inner and outer plexiform layers differentially control visual thresholds. iScience 0 41623460
2015 Characterization of the zebrafish cx36.7 gene promoter: Its regulation of cardiac-specific expression and skeletal muscle-specific repression. Gene 0 26692140

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