Ask about this productRelated genes to: GJD2 antibody
- Gene:
- GJD2 NIH gene
- Name:
- gap junction protein delta 2
- Previous symbol:
- GJA9
- Synonyms:
- CX36
- Chromosome:
- 15q14
- Locus Type:
- gene with protein product
- Date approved:
- 2007-01-16
- Date modifiied:
- 2016-10-05
Related products to: GJD2 antibody
Related articles to: GJD2 antibody
- Within the islets of Langerhans, gap junction coupling is important for synchronizing oscillatory free-calcium activity ([Ca2+]) and regulating pulsatile insulin release. In islets from multiple models of diabetes, gap junction coupling is disrupted, and [Ca2+] synchronization and pulsatile insulin is lost. Functional subpopulations have been identified within the islet that are linked to driving synchronized [Ca2+] and insulin release. These subpopulations can be disrupted under conditions associated with diabetes, such as glucolipotoxicity and inflammatory environments, and their loss may drive islet dysfunction. Here we investigated how loss of gap junction coupling influences functional subpopulations under diabetogenic environments. We treated islets with a cocktail of pro-inflammatory cytokines and protected gap junction coupling via co-treatment with a Cx36 peptide S293 that was previously shown to specifically prevent a decline in gap junction permeability and synchronized [Ca2+] dynamics. We performed calcium imaging and ChR2 stimulation and analyzed islet [Ca2+] dynamics and the presence of functional subpopulations, including hubs and first-responders. 1- or 24-h cytokine treatment disrupted gap junction coupling, which was fully prevented by S293 peptide co-treatment. Treatment with pro-inflammatory cytokines decreased the recruitment of [Ca2+] upon ChR2 stimulation, increased the time between first and last responding cells upon glucose stimulation, and reduced the number and consistency of hub cells. When preserving gap junction coupling by S293 during cytokine treatment, the presence and consistency of these subpopulations were only marginally improved. We therefore concluded that while gap junction coupling is important for functional subpopulations to exert their influence on islet function, the restoration of gap junctions alone is not sufficient to recover functional subpopulations under diabetogenic conditions. Thus, preventing a disruption to intrinsic β-cell properties that define functional subpopulations is likely important for preserving these subpopulations during diabetes. - Source: PubMed
Publication date: 2026/03/31
Levitt Claire HIsaacs DominicHansen Maria SKravets ViraBriggs Jennifer KBenninger Richard K P - Connexin36 (Cx36) is highly expressed in inhibitory and excitatory neurons as well as pancreatic β-cells, where it forms gap junction channels that coordinate metabolic and electrical responses. In addition, Cx36 forms hemichannels in pancreatic β-cells, where it may play a critical role in endocrine cell signaling. Despite this, the regulatory mechanisms and biophysical properties of Cx36 HCs remain poorly understood. Using HeLa cells lacking endogenous expression of large-pore channels and transfected with mouse Cx36-EGFP, we evaluated hemichannel activity through dye uptake assays and membrane current recordings. We found that Cx36 hemichannel activity is strongly inhibited by extracellular Mg, rather than Ca, in contrast to hemichannels formed by other connexins. Under reduced extracellular Mg, or under alkaline extracellular pH conditions, Cx36 hemichannels exhibited increased activity and allowed Ca influx, as detected by ratiometric dye FURA-2. Under low extracellular Mg conditions, Cx36 hemichannels exhibited increased permeability to small molecules and were blocked by La and quinine, but not by high glucose concentration. In-silico studies revealed interactions between Mg and two amino acid residues within a pore constriction (D47-E49), which alter the electrostatic potential of the hemichannel pore. Consistent with these observations, mutation of either amino acid residue to alanine (D47A or E49A) markedly reduced the inhibitory effect of extracellular Mg. Together, these findings offer critical insights into the regulation of Cx36 hemichannels and suggest that alterations in Mg homeostasis may have significant consequences for Cx36-mediated signaling. - Source: PubMed
Publication date: 2026/03/16
García AníbalMárquez-Miranda ValeriaBravo-Acuña NicolásAraya-Duran IngridRojas MaximilianoPalacios-Prado NicolásO'Brien JohnGonzález-Nilo Fernando DSáez Juan C - Small intestinal neuroendocrine tumors (SI-NETs) frequently present as multifocal lesions, but the molecular mechanisms underlying their development and heterogeneity remain unclear. This study aimed to characterize the phenotypes of tumor cell populations across anatomical sites in multifocal SI-NET patients and identify local microenvironmental factors influencing tumor development. - Source: PubMed
Publication date: 2026/03/04
Yogo AkitadaAkanuma NaokiKim Grace EMäkinen NettaThirlwell ChrissieNakakura Eric K - Drought and water scarcity, exacerbated by global warming, are enormous threats to global food sustainability and security. Poultry, in particular, are highly impacted by adverse environmental stressors. As nutrient absorption and intestinal integrity are critical for growth and performance, understanding the impact on the broiler gastrointestinal tract is highly relevant. Here, we examined the effect of chronic cyclic heat stress (HS) on the jejunal expression profile of tight-junction, gap-junction, adherens, and desmosome genes in the 4th generation of broiler lines divergently selected for low (LWE)- and high-water efficiency (HWE). Male HWE and LWE broilers (n = 240/line) were allotted to 12 environmental chambers (2 floor pens/chamber, 6 chambers/line, 20 birds/pen) and were exposed to cyclic HS (36°C for 9h/day from 9:00 am to 6:00 pm) or thermoneutral conditions (25°C) from day 29 to 49 of age in a 2 × 2 factorial design. Growth performance and mortality were recorded. At day 49, jejunal tissues were collected for molecular analyses using real-time quantitative PCR and immunoblot. Jejunal gene expression of multiple gut integrity factors were higher (P < 0.05) in the HWE as compared to the LWE lines, including claudin 22 (CLDN22), -34, occluding (OCDN), zona-occludin-2 (ZO-2), gap junction alpha1 (GJA1), GJA3, GJC1, and cadherin 1 (CDH1). CLDN8, -20, -25, -4, GJC2, and GJD2 were also greater (P < 0.05) in HWE, but were additionally downregulated (P < 0.05) during HS. Conversely PALS1-associated tight junction protein (PATJ) and desmocollin 1 (DSC1) mRNAs were significantly downregulated in the HWE as compared to the LWE broilers. Significant interactions between the line and environment were seen in CLDN1, where the expression was decreased in the LWE but increased in the HWE in HS. Additionally, CLDN15 and -16 genes were greatest in the HWE under TN conditions, while catenin alpha 2 (CTNNA2) was highest in the HWE during HS. Overall, the jejunal expression profile of key genes associated with intestinal barrier integrity likely contributes to the water efficiency phenotype and the response of these birds to HS. - Source: PubMed
Publication date: 2025/12/16
Greene Elizabeth SOrlowski SaraDridi Sami - The output mitral cells (MCs) and tufted cells (TCs) of the mammalian olfactory bulb (OB) are coupled through both chemical mechanisms as well as gap junctions that are mediated by connexin 36 (Cx36). Here, we tested both behavioural and physiological effects of eliminating gap junctions in knockout (KO) mice with homozygous deletions of Cx36. In a go/no-go associative learning task, Cx36 KO mice were found to display reduced discrimination capabilities when presented with pairs of stimuli that included a monomolecular odour and mixtures that had the same monomolecular odour and a small amount of a structurally similar odour. The impairments did not occur for less similar odour pairs, suggesting that Cx36 KO mice have olfactory processing deficits that are specific to fine odour discrimination. In physiological recordings in OB slices from Cx36 KO mice, MCs displayed reduced excitation in response to electrical stimulation of sensory afferents, both single stimulus pulses as well as a theta burst pattern designed to mimic sniffing. The reduction in MC excitatory current was most prominent for late portions of their response, 300 ms after single stimulus pulses or following all theta bursts that came after the first. More global local field potentials recorded in OB glomeruli were largely unaffected by Cx36 KO. We suggest that the KO-induced impairments in fine odour discrimination could be linked to reduced late-phase MC excitation because of the longer time that mice require to make difficult odour discriminations. KEY POINTS: The output mitral cells (MCs) of the olfactory bulb (OB) engage in strong electrical coupling via connexin 36 (Cx36)-mediated gap junctions. However, the behavioural and physiological relevance of these gap junctions is not well understood. In studies conducted in Cx36 knockout (KO) mice, we found impaired odour discrimination vs. wild-type mice in a go/no-go associative learning task, although deficits only occurred with the most difficult tasks involving odour mixtures. These results provide the first evidence to date of olfactory behavioural deficits in Cx36 KO mice. In OB slices, Cx36 KO reduced excitatory responses in MCs to electrical stimulation of sensory afferents, but only during latter stages of the response. We suggest that KO-induced impairments in fine odour discrimination could be linked to reduced late-phase MC excitation because of the longer time that mice require to make difficult odour discriminations. - Source: PubMed
Publication date: 2025/12/10
Kuruppath PraveenJones Shelly TPouille FredericRamirez-Gordillo DanielRestrepo DiegoSchoppa Nathan E