Psychiatry related information on GJA9

• No variant exclusively cosegregates with the disease in a large pedigree that mainly supports the chromosome 15q14 locus, providing evidence that CX36 is not causative for the pathogenesis of catatonic schizophrenia in this family [1].

High impact information on GJA9

• Quinine thus offers a potentially useful method to block certain types of gap junction channels, including those between neurons that are formed by Cx36 [2].
• Our data indicate an important role for Cx36-gap junctions in modulating stimulation threshold and kinetics of insulin release [3].
• With closed ATP-sensitive K(+) (K(ATP)) channels, the electrically coupled beta-cells of Cx36(+/+) and Cx36(+/-) mice were hyperpolarized by the membrane potential of adjacent, inactive cells [3].
• In order to identify the molecular mechanisms that control the beta-cell expression of Cx36, we initiated the characterization of the human 5' regulatory region of the CX36 gene [4].
• A 2043-bp fragment of the human CX36 promoter was identified from a human BAC library and fused to a luciferase reporter gene [4].

Biological context of GJA9

• The human orthologue CX36 is located on chromosome 15q14, a region recently shown to contain a susceptibility gene for hereditary catatonic schizophrenia [1].
• Three polymorphic sites within CX36 were found by sequencing the two exons, the intron-exon boundaries and the putative promoter region of the gene derived from patients and control subjects [1].
• VTA GABA neurons recorded via whole-cell patch clamp in the midbrain slice preparation of P25-50 rats showed robust expression of Cx36 transcripts when tested with single-cell quantitative reverse transcription polymerase chain reaction [5].
• Additionally, in at least 3 mouse and human connexin genes (mCx36, mCx39, mCx57 and hCx31.3, hCx36, as well as hCx40.1) the reading frame is spliced together from 2 different exons [6].

Anatomical context of GJA9

• Rat connexin-36 (Cx36) is the first gap junction protein shown to be expressed predominantly in neuronal cells of the mammalian central nervous system [7].
• The distribution of Cx36 in several regions of the human central nervous system is similar to that previously observed in rat brain [7].
• Compared to implanted non-stimulated controls, a significant decrease in Cx36 expression was observed in the stimulated dorsal hippocampus at 3h post-stimulation, which returned to control levels by 24h [8].
• Cx36 is the predominant connexin isoform expressed by pancreatic beta-cells [9].
• To address this question, we searched for a cell line expressing Cx36 and having glucose-induced insulin secretion comparable to that of primary beta-cells [9].

Associations of GJA9 with chemical compounds

• The Cx36 GJ blocker mefloquine (30 mg/kg) suppressed VTA GABA neuron ICPSDs in mature freely behaving rats [5].
• Thus, mature VTA GABA neurons appear to be connected by electrical synapses via Cx36 GJs, whose coupling is enhanced by corticotegmental input and by dopamine [5].
• The identification of this permselectivity is expected to facilitate the identification of endogenous permeant molecules and of the mechanism whereby Cx36 signalling significantly contributes to the modulation of insulin secretion [10].

Other interactions of GJA9

• Moreover, we excluded three candidate genes, CKTSF1B1, KLF13 and CX36 [11].
• For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group [12].
• CONCLUSIONS: The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis [12].
• This paper describes how a fluorescent nuclear tracer, Po-pro-1, can be used to visualize coupled cells in several types of retinal neurons thought to be comprised of different connexin proteins including Cx36, Cx45, Cx50, and Cx57 [13].

Analytical, diagnostic and therapeutic context of GJA9

• As a prerequisite for studies devoted to the investigation of the possible role of this connexin in human neurological diseases, we report the cloning and sequencing of the human Cx36 gene, its chromosomal localization, and its pattern of expression in the human brain analyzed by radioactive in situ hybridization [7].

References