Innexin Gap Junctions

Drosophila innexins - inx3


inx3 is located at position 98E6-98F1 on the third chromosome. It is expressed in the oocyte (Stebbings et al, 2002, Bohrmann and Zimmermann, 2008), in a broad pattern in the embryo (Stebbings et al, 2002, Inx3 in a wild type embryo), in larval (Inx3 in the wing disc) and pupal tissues and in the adult ( least in the central nervous system Stebbings et al, 2002, Inx3 in the optic lobe). Using the Xenopus oocyte system it has been shown that Inx3 protein is not able to form homomeric, homotypic (channels composed only of Inx3) gap junction intercellular channels but can form intercellular channels in the presence of Inx2 (Stebbings et al, 2000). A growing list of observations strongly suggest an interaction between Inx3 and Inx2 in vivo; 1/ These subunits exhibit broadly overlapping expression patterns in the developing animal (Stebbings et al, 2002), 2/ Both subunits co-localise in gap junction plaques in certain tissues (Lehmann et al, 2006), 3/ Inx3 becomes mislocalised in inx2 mutants (see Inx3 in inx2null and Inx3 in Inx2Dominant compared to Inx3 in wild type) and Inx2 protein is mislocalised when Inx3 levels are knocked down (Lehmann et al, 2006)(also see Rescue of Inx3 distribution in an inx2null embryo), 4/ co-immunoprecipitation experiments using antibodies for Inx3 also pull down Inx2, but only when the C-terminal of Inx2 is not sterically impeded by addition of GFP (Lehmann et al, 2006), 5/ The C-terminal tail of Inx3 can interact directly with the C-tail of Inx2 (Lehmann et al, 2006), 6/ Expressing a snap-back RNAi construct to knockdown Inx3 levels produces phenotypes, eg. holes in the epidermis, similar to those observed in inx2 mutants (Lehmann et al, 2006), 7/ co-expression of UAS-inx3 and UAS-inx2 results stronger phenotypes than expression of either UAS-innexin alone (Stebbings et al, 2000) (however, co-expressing many combinations of UAS-innexin ….even using multiple copies of the same UAS-innexin… can achieve this, so it’s not straightforward to draw conclusions from such experiments …. see Expressing multiple UAS-innexins in the developing wing and related images). Although Inx3 and Inx2 can co-localise at gap junction plaques in vivo only a fraction of the available subunits appear to do so. Plaques have been observed where Inx2 and Inx3 do not appear to co-localise (Lehmann et al, 2006) suggesting that Inx3 might interact with innexin subunits other than Inx2, or form homomeric plaques that are not involved in intercellular communication (…cell adhesion instead?). Inx3 and Ogre are both expressed in pupal salivary glands and transgenically expressed myc-tagged Ogre co-localises with Inx3 in both plaques and putative annular junctions, although, the relative amount of each innexin subunit (as quantified by fluorescent intensity) varies amongst annular junction vesicles (see Manipulating innexin protein subunit levels).

   It would be convenient to assume that Inx3 has similar properties and roles to those of Inx2 due to the points listed above, however, in addition to the fact that Inx3 and Inx2 do not always co-localise, there are two other observations that suggest Inx3 may have special/different functional properties than Inx2. Firstly, injecting oocytes with antibodies against Inx3 produces relatively small changes in gap junction mediated dye transfer between cells compared injection of antibodies directed against Inx2 (Bohrmann and Zimmermann, 2008). Although one could attribute this to different diffusion properties of the antibodies or targeting of different innexin domains, it is also possible that Inx2 and Inx3 mediate different roles in the oocyte. Secondly, using a technique that quantifies peptide interactions (surface plasmon resonance, Lehmann et al, 2006) the C-terminal tail of Inx3 was found to interact with the Inx3 intracellular loop and the N-terminal sequence, whereas, the Inx3 C-tail only interacts strongly with the C-terminus of Inx2. Inx3 may have a role in regulating gap junction channels by means of intra- or inter-molecular interactions between its intracellular domains. Inx2 may not possess this property.

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(Publications prior to 2009 are based on data extracted from the textpresso text mining facility.)

Phenotypic plasticity and genotype by environment interaction for olfactory behavior in Drosophila melanogaster., Genetics, Sambandan D, Carbone MA, Anholt RR, Mackay TF., 2008, 179(2):1079-88 pubmed/NLM

Cross regulation of intercellular gap junction communication and paracrine signaling pathways during organogenesis in Drosophila., Dev Biol., Lechner H, Josten F, Fuss B, Bauer R, Hoch M., 2007, 310(1):23-34 pubmed/NLM

Dynamic genetic interactions determine odor-guided behavior in Drosophila melanogaster., Genetics, Sambandan D, Yamamoto A, Fanara JJ, Mackay TF, Anholt RR., 2006, 174(3):1349-63 pubmed/NLM

Heteromerization of innexin gap junction proteins regulates epithelial tissue organization in Drosophila., Mol Biol Cell., Lehmann C, Lechner H, Löer B, Knieps M, Herrmann S, Famulok M, Bauer R, Hoch M., 2006, 17(4):1676-85 pubmed/NLM

A possible flip-flop genetic mechanism for reciprocal gene expression., FEBS Lett., Chiusano ML, Di Giaimo R, Potenza N, Russo GM, Geraci G, del Gaudio R., 2005, 579(22):4919-22 pubmed/NLM

Intercellular communication: the Drosophila innexin multiprotein family of gap junction proteins., Chem Biol., Bauer R, Loer B, Ostrowski K, Martini J, Weimbs A, Lechner H, Hoch M., 2005, 12(5):515-26 pubmed/NLM

Gap junction channel protein innexin 2 is essential for epithelial morphogenesis in the Drosophila embryo., Mol Biol Cell., Bauer R, Lehmann C, Martini J, Eckardt F, Hoch M., 2004, 15(6):2992-3004 pubmed/NLM

The Drosophila gap junction channel gene innexin 2 controls foregut development in response to Wingless signalling., J Cell Sci., Bauer R, Lehmann C, Fuss B, Eckardt F, Hoch M., 2002, 115(Pt 9):1859-67 pubmed/NLM

Gap junctions in Drosophila: developmental expression of the entire innexin gene family., Mech Dev., Stebbings LA, Todman MG, Phillips R, Greer CE, Tam J, Phelan P, Jacobs K, Bacon JP, Davies JA., 2002, 113(2):197-205 pubmed/NLM

A germline-specific gap junction protein required for survival of differentiating early germ cells., Development, Tazuke SI, Schulz C, Gilboa L, Fogarty M, Mahowald AP, Guichet A, Ephrussi A, Wood CG, Lehmann R, Fuller MT., 2002, 129(10):2529-39 pubmed/NLM

Identification of novel Drosophila neural precursor genes using a differential embryonic head cDNA screen., Mech. Dev., Brody T., Stivers C., Nagle J., Odenwald WF., 2002, 113(1):41-59 pubmed/NLM

A P-insertion screen identifying novel X-linked essential genes in Drosophila., Mech Dev., Bourbon HM, Gonzy-Treboul G, Peronnet F, Alin MF, Ardourel C, Benassayag C, Cribbs D, Deutsch J, Ferrer P, Haenlin M, Lepesant JA, Noselli S, Vincent A., 2002, 110(1-2):71-83 pubmed/NLM

Innexins get into the gap., Bioessays, Phelan P, Starich TA., 2001, 23(5):388-96 pubmed/NLM

Gastrointestinal development in the Drosophila embryo requires the activity of innexin gap junction channel proteins., Cell Commun Adhes., Bauer R, Lehmann C, Hoch M., 2001, 8(4-6):307-10 pubmed/NLM

Two Drosophila innexins are expressed in overlapping domains and cooperate to form gap-junction channels., Mol Biol Cell., Stebbings LA, Todman MG, Phelan P, Bacon JP, Davies JA., 2000, 11(7):2459-70 pubmed/NLM

Drosophila has several genes for gap junction proteins., Gene, Curtin KD, Zhang Z, Wyman RJ., 1999, 232(2):191-201 pubmed/NLM

A genetic screen of the Drosophila X chromosome for mutations that modify Deformed function., Genetics, Florence B, McGinnis W., 1998, 150(4):1497-511 pubmed/NLM

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