Disease relevance of Gja3

• New genetic model rat for congenital cataracts due to a connexin 46 (Gja3 ) mutation [1].

High impact information on Gja3

• Oocytes that have synthesized Cx46 depolarize and lyse within 24 h, a phenomenon never observed after expression of rat connexins 32 or 43 (Cx32 and Cx43) [2].
• Unlike other connexins expressed in Xenopus oocytes, these results suggest that unprocessed Cx46 induces nonselective channels in the oolemma that are voltage dependent and opened by large depolarizations [2].
• Synthesis of Cx46 in either reticulocyte lysate or Xenopus oocytes yields a 46-kD polypeptide; all anti-Cx46 antisera recognize a protein in rat lens membranes 5-10 kD larger, suggesting substantive lenticular posttranslational processing of the native translation product [2].
• One mechanism partially closes Cx46 hemichannels from a fully open state, gammaopen, to a substate, gammasub, about one-third of the conductance of gammaopen; these transitions occur when the cell is depolarized to inside positive voltages, consistent with gating by transjunctional voltage in Cx46 gap junctions [3].
• Cx46 hemichannels display a substantial preference for cations over anions, yet have a large unitary conductance (approximately 300 pS) and a relatively large pore as inferred from permeability to tetraethylammonium (approximately 8.5 angstroms diameter) [3].

Biological context of Gja3

• These results suggest that alteration of gap junction function (as evidenced by the change in phosphorylation of Cx46) may be associated with the development of the selenite cataract, but that neither Cx46 nor Cx50 is subject to the well-characterized proteolysis associated with the selenite cataract model [4].
• However, by 3 days after crush injury, coincident with changes in Schwann cell phenotype, Cx46 mRNA rapidly increased in the degenerating regions [5].
• Loop- and tail-specific Cx46 antibodies were used to identify regions of posttranslational modification [6].
• During rat embryonic development, the more rapidly migrating, nonphosphorylated form of Cx46 was prevalent at 15 days gestation; as development progressed, there was a loss of the nonphosphorylated form with a concomitant increase in the phosphorylated form, such that by 28 days after birth only the phosphorylated form was detectable [7].

Anatomical context of Gja3

• The purpose of this work was to determine if the lens gap junction proteins connexin 46 (Cx46) and connexin 50 (Cx50) were altered with the development of selenite-induced cataract [4].
• A 56/58-kDa connexin46 (Cx46) protein species was detected in adult rat sciatic nerve, along with very low levels of Cx46 mRNA [5].
• These results suggest that enhanced expression of Cx46 and Cx43, by nonneuronal cells, may be important for the injury and regenerative responses of peripheral nerves [5].
• Additionally, the 56/58-kDa Cx46 protein species present in adult nerve decreased and a 53-kDa Cx46 species, which was also present in cultured Schwann cells, became apparent [5].
• An immunohistochemical analysis using connexin- specific antibodies revealed that migrating rat neural crest cells express the gap junction constituents connexins 43 (Cx 43) and Cx 46 [8].

Associations of Gja3 with chemical compounds

• Analyses of reciprocal chimeric hemichannels that swap NH2- and COOH-terminal halves of Cx46 and Cx50 demonstrate that the difference in regulation by monovalent ions in these connexins resides in the NH2-terminal half [9].
• Connexin 46 and connexin 50 in selenite cataract [4].
• Aliquots of urea-insoluble protein from membrane fractions were analyzed by quantitative densitometry of Western blots probed with antibodies to Cx46 and Cx50 [4].
• Cx46 was phosphorylated on both serine and threonine [10].
• CONCLUSIONS: Activation of PKCgamma by H2O2 stimulated differential Ser phosphorylation of Cx50 versus Cx46, within lipid rafts [11].

Regulatory relationships of Gja3

• PURPOSE: To identify the role of PKC-gamma in control of and phosphorylation of connexin 46 (Cx46) in the lens cortex [10].

Other interactions of Gja3

• Voltage-gated whole cell currents are measured in oocytes injected with dilute concentrations of Cx46 but not Cx43 mRNA [2].
• PKC-gamma phosphorylation of connexin 46 in the lens cortex [10].

Analytical, diagnostic and therapeutic context of Gja3

• Similarly, in organ culture of bovine lenses, Cx46 could be labeled with 35S-methionine, but the immunoprecipitated material remained in the rapidly migrating form for 1 week, the longest time measured [7].
• Lipid raft-localization of PKCgamma, Cx46, or Cx50 was demonstrated by immunoblotting [11].
• METHODS: The association between PKC-gamma and Cx46 was determined by co-immunoprecipitation from whole lens [10].
• Quantitative RT-PCR indicates that Cx37, Cx45, and Cx46 are preferentially expressed during early renal development [12].

References