[en] Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is the last identified member of the inositol 1,4,5-trisphosphate 3-kinases family which phosphorylates inositol 1,4,5-trisphosphate into inositol 1,3,4,5-tetrakisphosphate. Although expression and function of the two other family members ITPKA and ITPKB are rather well characterized, similar information is lacking for ITPKC. Here, we first defined the expression of Itpkc mRNA and protein in mouse tissues and cells using in situ hybridization and new antibodies. Surprisingly, we found that cells positive for ITPKC in the studied tissues express either a multicilium (tracheal and bronchial epithelia, brain ependymal cells), microvilli forming a brush border (small and large intestine, and kidney proximal tubule cells) or a flagellum (spermatozoa), suggesting a role for ITPKC either in the development or the function of these specialized cellular structures. Given this surprising expression, we then analyzed ITPKC function in multiciliated tracheal epithelial cells and sperm cells using our Itpkc knock-out mouse model. Unfortunately, no significant difference was observed between control and mutant mice for any of the parameters tested, leaving the exact in vivo function of this third Ins(1,4,5)P3 3-kinase still open.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Scoumanne, Ariane ; Université de Liège - ULiège > GIGA-R : Labo de génétique fonctionnelle
Burgner, D., Davila, S., Breunis, W.B., Ng, S.B., Li, Y., Bonnard, C., Ling, L., Wright, V.J., Thalamuthu, A., Odam, M., Shimizu, C., Burns, J.C., Levin, M., Kuijpers, T.W., Hibberd, M.L., International Kawasaki Disease Genetics Consortium. A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease. PLoS Genet., 5, 2009, e1000319.
Burnett, L.A., Anderson, D.M., Rawls, A., Bieber, A.L., Chandler, D.E., Mouse sperm exhibit chemotaxis to allurin, a truncated member of the cysteine-rich secretory protein family. Dev. Biol. 360 (2011), 318–328.
Choi, K.Y., Kim, H.K., Lee, S.Y., Moon, K.H., Sim, S.S., Kim, J.W., Chung, H.K., Rhee, S.G., Molecular cloning and expression of a complementary DNA for inositol 1,4,5-trisphosphate 3-kinase. Science 248 (1990), 64–66.
Communi, D., Vanweyenberg, V., Erneux, C., D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium:calmodulin-dependent protein kinase II phosphorylation mechanism. EMBO J. 16 (1997), 1943–1952.
Dewaste, V., Pouillon, V., Moreau, C., Shears, S., Takazawa, K., Erneux, C., Cloning and expression of a cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase C. Biochem. J. 352 (2000), 343–351.
Erneux, C., Ghosh, S., Koenig, S., Inositol(1,4,5)P3 3-kinase isoenzymes: catalytic properties and importance of targeting to F-actin to understand function. Adv. Biol. Regul. 60 (2016), 135–143.
Fukuda, N., Yomogida, K., Okabe, M., Touhara, K., Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility. J. Cell. Sci. 117 (2004), 5835–5845.
Hata, A., Onouchi, Y., Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine. J. Hum. Genet. 54 (2009), 67–73.
Khor, C.C., Davila, S., Breunis, W.B., Lee, Y.C., Shimizu, C., Wright, V.J., Yeung, R.S., Tan, D.E., Sim, K.S., Wang, J.J., Wong, T.Y., Pang, J., Mitchell, P., Cimaz, R., Dahdah, N., Cheung, Y.F., Huang, G.Y., Yang, W., Park, I.S., Lee, J.K., Wu, J.Y., Levin, M., Burns, J.C., Burgner, D., Kuijpers, T.W., Hibberd, M.L. Hong Kong–Shanghai Kawasaki Disease Genetics Consortium Korean Kawasaki Disease Genetics Consortium Taiwan Kawasaki Disease Genetics Consortium International Kawasaki Disease Genetics Consortium US Kawasaki Disease Genetics Consortium, Blue Mountains Eye Study. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat. Genet. 43 (2011), 1241–1246.
Kuo, H.C., Yang, K.D., Juo, S.H., Liang, C.D., Chen, W.C., Wang, Y.S., Lee, C.H., His, E., Yu, H.R., Woon, P.Y., Lin, I.C., Huang, C.F., Hwang, D.Y., Lee, C.P., Lin, L.Y., Chang, W.P., Chang, W.C., ITPKC single nucleotide polymorphism associated with the Kawasaki disease in a Taiwanese population. PLoS One, 6, 2011, e17370.
Lin, M.T., Wang, J.K., Yeh, J.I., Sun, L.C., Chen, P.L., Wu, J.F., Chang, C.C., Lee, W.L., Shen, C.T., Wang, N.K., Wu, C.S., Yeh, S.Z., Chen, C.A., Chiu, S.N., Wu, M.H., Clinical implication of the C allele of the Itpkc gene SNP rs28493229 in Kawasaki disease. Pediatr. Infect. Dis. J. 30 (2011), 148–152.
Nalaskowski, M.M., Bertsch, U., Fanick, W., Stockebrand, M.C., Schmale, H., Mayr, G.W., Rat inositol 1,4,5-trisphosphate 3-kinase C is enzymatically specialized for basal cellular inositol trisphosphate phosphorylation and shuttles actively between nucleus and cytoplasm. J. Biol. Chem. 278 (2003), 19765–19776.
Nalaskowski, M.M., Windhorst, S., Stockebrand, M.C., Mayr, G.W., Subcellular localisation of human inositol 1,4,5-trisphosphate 3-kinase C: species-specific use of alternative export sites for nucleo-cytoplasmic shuttling indicates divergent roles of the catalytic and N-terminal domains. Biol. Chem. 387 (2006), 583–593.
Onouchi, Y., Gunji, T., Burns, J.C., Shimizu, C., Newburger, J.W., Yashiro, M., Nakamura, Y., Yanagawa, H., Wakui, K., Fukushima, Y., Kishi, F., Hamamoto, K., Terai, M., Sato, Y., Ouchi, K., Saji, T., Nariai, A., Kaburagi, Y., Yoshikawa, T., Suzuki, K., Tanaka, T., Nagai, T., Cho, H., Fujino, A., Sekine, A., Nakamichi, R., Tsunoda, T., Kawasaki, T., Nakamura, Y., Hata, A., ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat. Genet. 40 (2008), 35–42.
Onouchi, Y., Suzuki, Y., Suzuki, H., Terai, M., Yasukawa, K., Hamada, H., Suenaga, T., Honda, T., Honda, A., Kobayashi, H., Takeuchi, T., Yoshikawa, N., Sato, J., Shibuta, S., Miyawaki, M., Oishi, K., Yamaga, H., Aoyagi, N., Iwahashi, S., Miyashita, R., Murata, Y., Ebata, R., Higashi, K., Ozaki, K., Sasago, K., Tanaka, T., Hata, A., ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease. Pharmacogenomics J. 13 (2013), 52–59.
Peng, Q., Chen, C., Zhang, Y., He, H., Wu, Q., Liao, J., Li, B., Luo, C., Hu, X., Zheng, Z., Yang, Y., Single-nucleotide polymorphism rs2290692 in the 3′UTR of ITPKC associated with susceptibility to Kawasaki disease in a Han Chinese population. Pediatr. Cardiol. 33 (2012), 1046–1053.
Pouillon, V., Hascakova-Bartova, R., Pajak, B., Adam, E., Bex, F., Dewaste, V., Van Lint, C., Leo, O., Erneux, C., Schurmans, S., Inositol 1,3,4,5-tetrakisphosphate is essential for T lymphocyte development. Nat. Immunol. 4 (2003), 1136–1143.
Pouillon, V., Maréchal, Y., Frippiat, C., Erneux, C., Schurmans, S., Inositol 1,4,5-trisphosphate 3-kinase B (Itpkb) controls survival, proliferation and cytokine production in mouse peripheral T cells. Adv. Biol. Regul. 53 (2013), 39–50.
Saiardi, A., Caffrey, J.J., Snyder, S.H., Shears, S.B., Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett. 468 (2000), 28–32.
Schurmans, S., Pouillon, V., Maréchal, Y., Regulation of B cell survival, development and function by inositol 1,4,5-trisphosphate 3-kinase B (Itpkb). Adv. Enzyme Regul. 51 (2011), 66–73.
Schurmans, S., Polizzi, S., Scoumanne, A., Sayyed, S., Molina-Ortiz, P., The Ras/Rap GTPase activating protein RASA3: from gene structure to in vivo functions. Adv. Biol. Regul. 5 (2015), 153–161.
Takazawa, K., Lemos, M., Delvaux, A., Lejeune, C., Dumont, J.E., Erneux, C., Rat brain inositol 1,4,5-trisphosphate 3-kinase. Ca2+-sensitivity, purification and antibody production. Biochem. J. 268 (1990), 213–217.
Takazawa, K., Perret, J., Dumont, J.E., Erneux, C., Molecular cloning and expression of a new putative inositol 1,4,5-trisphosphate 3-kinase isoenzyme. Biochem. J. 278 (1991), 883–886.
Vanweyenberg, V., Communi, D., D'Santos, C.S., Erneux, C., Tissue- and cell-specific expression of Ins(1,4,5)P3 3-kinase isoenzymes. Biochem. 306 (1995), 429–435.
York, J.D., Regulation of nuclear processes by inositol polyphosphates. Biochim. Biophys. Acta 1761 (2006), 552–559.
You, Y., Richer, E.J., Huang, T., Brody, S.L., Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population. Am. J. Physiol. Lung Cell. Mol. Physiol. 283 (2002), L1315–L1321.
