Abstract
Copine1 is a ubiquitously expressed protein found in various tissues including the brain, but little is known about the physiological function of this protein. Here, we showed that copine1 is involved in neuronal differentiation. Over-expression of copine1 clearly increased neurite outgrowth and expression of Tuj1, a neuronal marker protein, in HiB5 cells. In addition, endogenous copine1 was transiently increased at the early time during neuronal differentiation of HiB5 cells. When the expression of endogenous copine1 was knocked-down by its specific shRNA, PDGF-mediated neurite outgrowth was clearly decreased in HiB5 cells. Furthermore, over-expression of copine1 increased phosphorylation of Akt and copine1-specific shRNA decreased phosphorylation of Akt during neuronal differentiation of HiB5 cells. Interestingly, the phosphorylation level of PI3K, generally known as an upstream protein of Akt, was not changed by copine1 expression. These results suggest that copine1 enhances neuronal differentiation of HiB5 cells not through the PI3K-Akt pathway, but by using another Akt activated signal pathway.
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Chung, J.J., Cho, S., Kwon, Y.K., Kim, D.H., and Kim, K. (2000). Activation of retinoic acid receptor gamma induces proliferation of immortalized hippocampal progenitor cells. Brain Res. Mol. Brain Res. 83, 52–62.
Creutz, C.E., Tomsig, J.L., Snyder, S.L., Gautier, M.C., Skouri, F., Beisson, J., and Cohen, J. (1998). The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans. J. Biol. Chem. 273, 1393–402.
Ditlevsen, D.K., Køhler, L.B., Pedersen, M.V., Risell, M., Kolkova, K., Meyer, M., Berezin, V., and Bock, E. (2003) The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival. J. Neurochem. 84, 546–556.
Jiménez, N., and Hernández-Cruz, A. (2001). Modifications of intracellular Ca2+ signalling during nerve growth factor-induced neuronal differentiation of rat adrenal chromaffin cells. Eur. J. Neurosci. 13, 1487–1500.
Joung, I., Kim, H.J., and Kwon, Y.K. (2005). p62 modulates Akt activity via association with PKCzeta in neuronal survival and differentiation. Biochem. Biophys. Res. Commun. 334, 654–660.
Kim, G., Choe, Y., Park, J., Cho, S., and Kim, K. (2002). Activation of protein kinase A induces neuronal differentiation of HiB5 hippocampal progenitor cells. Brain Res. Mol. Brain Res. 109, 134–145.
Ku, B.M., Lee, Y.K., Jeong, J.Y., Ryu, J., Choi, J., Kim, J.S., Cho, Y. W., Roh, G.S., Kim, H.J., Cho, G.J., et al. (2011). Caffeine inhibits cell proliferation and regulates PKA/GSK3β pathways in U87MG human glioma cells. Mol. Cells 31, 275–279.
Maitra, R., Grigoryev, D.N., Bera, T.K., Pastan, I.H., and Lee, B. (2003). Cloning, molecular characterization, and expression analysis of Copine 8. Biochem. Biophys. Res. Commun. 303, 842–847.
Manning, B.D., and Cantley, L.C. (2007). AKT/PKB signaling: navigating downstream. Cell 129, 1261–1274.
Moore, S.F., Hunter, R.W., and Hers, I. (2011). mTORC2 protein complex-mediated Akt (Protein Kinase B) Serine 473 Phosphorylation is not required for Akt1 activity in human platelets. J. Biol. Chem. 286, 24553–24560.
Oishi, K., Watatani, K., Itoh, Y., Okano, H., Guillemot, F., Nakajima, K., and Gotoh, Y. (2009). Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1. Proc. Natl. Acad. Sci. USA 106, 13064–13069.
Palazuelos, J., Ortega, Z., Díaz-Alonso, J., Guzmán, M., and Galve-Roperh, I. (2012). CB2 cannabinoid receptors promote neural progenitor cell proliferation via mTORC1 signaling. J. Biol. Chem. 287, 1198–1209.
Park, J.Y., Hwang, E.M., Park, N., Kim, E., Kim, D.G., Kang, D., Han, J., Choi, W.S., Ryu, P.D., and Hong, S.G. (2007). Gateway RFP-fusion vectors for high throughput functional analysis of genes. Mol. Cell 23, 357–362.
Perestenko, P.V., Pooler, A.M., Noorbakhshnia, M., Gray, A., Bauccio, C., and Jeffrey McIlhinney, R.A. (2010). Copines-1, -2, -3, -6 and -7 show different calcium-dependent intracellular membrane translocation and targeting. FEBS J. 277, 5174–5189.
Persad, S., Attwell, S., Gray, V., Mawji, N., Deng, J.T., Leung, D., Yan, J., Sanghera, J., Walsh, M.P., and Dedhar, S. (2001). Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J. Biol. Chem. 276, 27462–27469.
Ramsey, C.S., Yeung, F., Stoddard, P.B., Li, D., Creutz, C.E., and Mayo, M.W. (2008). Copine-I represses NF-kappaB transcription by endoproteolysis of p65. Oncogene 27, 3516–3526.
Read, D.E., and Gorman, A.M. (2009). Involvement of Akt in neurite outgrowth. Cell. Mol. Life Sci. 66, 2975–2984.
Tomsig, J.L., and Creutz, C.E. (2002). Copines: a ubiquitous family of Ca(2+)-dependent phospholipid-binding proteins. Cell. Mol. Life Sci. 59, 1467–1477.
Tomsig, J.L., Snyder, S.L., and Creutz, C.E. (2003). Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif. J. Biol. Chem. 278, 10048–10054.
Tomsig, J.L., Sohma, H., and Creutz, C.E. (2004). Calcium-dependent regulation of tumour necrosis factor-alpha receptor signaling by copine. Biochem. J. 378, 1089–1094.
Yang, L., Qiao, G., Ying, H., Zhang, J., and Yin, F. (2010). TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha. Biochem. Biophys. Res. Commun. 400, 16–20.
Zhang, D., and Aravind, L. (2010). Identification of novel families and classification of the C2 domain superfamily elucidate the origin and evolution of membrane targeting activities in eukaryotes. Gene 469, 18–30.
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Park, N., Yoo, J.C., Ryu, J. et al. Copine1 enhances neuronal differentiation of the hippocampal progenitor HiB5 cells. Mol Cells 34, 549–554 (2012). https://doi.org/10.1007/s10059-012-0235-7
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DOI: https://doi.org/10.1007/s10059-012-0235-7