KIAA1199: a novel regulator of MEK/ERK-induced Schwann cell dedifferentiation

[en] The molecular mechanisms that regulate Schwann cell (SC) plasticity and the role of the Nrg1/ErbB-induced MEK1/ERK1/2 signalling pathway in SC dedifferentiation or in myelination remain unclear. It is currently believed that different levels of MEK1/ERK1/2 activation define the state of SC differentiation. Thus, the identification of new regulators of MEK1/ERK1/2 signalling could help to decipher the context-specific aspects driving the effects of this pathway on SC plasticity. In this perspective, we have investigated the potential role of KIAA1199, a protein that promotes ErbB and MEK1/ERK1/2 signalling in cancer cells, in SC plasticity. We depleted KIAA1199 in the SC-derived MSC80 cell line with RNA-interference-based strategy and also generated Tamoxifen-inducible and conditional mouse models in which KIAA1199 is inactivated through homologous recombination, using the Cre-lox technology. We show that the invalidation of KIAA1199 in SC decreases the expression of cJun and other negative regulators of myelination and elevates Krox20, driving them towards a pro-myelinating phenotype. We further show that in dedifferentiation conditions, SC invalidated for KIAA1199 exhibit lower myelin clearance as well as increased myelination capacity. Finally, the Nrg1-induced activation of the MEK/ERK/1/2 pathway is severely reduced when KIAA1199 is absent, indicating that KIAA1199 promotes Nrg1-dependent MEK1 and ERK1/2 activation in SCs. In conclusion, this work identifies KIAA1199 as a novel regulator of MEK/ERK-induced SC dedifferentiation and contributes to a better understanding of the molecular control of SC dedifferentiation.

Research Center/Unit :

Giga-Neurosciences et GIGA Molecular Biology of Diseases

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology
Biochemistry, biophysics & molecular biology

Author, co-author :

Boerboom, Angelique; Université de Liège - ULiège > Département des Sciences biomédicales et précliniques

Reusch, Céline ; Université de Liège > GIGA-Research

Pieltain, Alexandra ; Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

Chariot, Alain ; Université de Liège > Département de pharmacie > Chimie médicale

Franzen, Rachelle ; Université de Liège > Département des sciences biomédicales et précliniques > Neuro-anatomie

Language :

English

Title :

KIAA1199: a novel regulator of MEK/ERK-induced Schwann cell dedifferentiation

Publication date :

October 2017

Journal title :

Glia

ISSN :

0894-1491

eISSN :

1098-1136

Publisher :

Wiley Liss, Inc., New York, United States - New York

Volume :

Issue :

Pages :

1682-1696

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

since 27 July 2017

Statistics

Number of views

343 (36 by ULiège)

Number of downloads

516 (24 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Abe, S., Usami, S., & Nakamura, Y. (2003). Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed in Deiters' cells and the fibrocytes, as the cause of nonsyndromic hearing loss. Journal of Human Genetics, 48, 564–570.
Adams, K. W., Kletsov, S., Lamm, R. J., Elman, J. S., Mullenbrock, S., & Cooper, G. M. (2017). Role for Egr1 in the transcriptional program associated with neuronal differentiation of PC12 cells. PLoS One, 12, e0170076-
Amin, D. N., Tuck, D., & Stern, D. F. (2005). Neuregulin-regulated gene expression in mammary carcinoma cells. Experimental Cell Research, 309, 12–23.
Arthur-Farraj, P. J., Latouche, M., Wilton, D. K., Quintes, S., Chabrol, E., Banerjee, A., Woodhoo, A., Jenkins, B., Rahman, M., Turmaine, M., Wicher, G. K., Mitter, R., Greensmith, L., Behrens, A., Raivich, G., Mirsky, R., & Jessen, K. R. (2012). c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron, 75, 633–647.
Atanasoski, S., Scherer, S. S., Sirkowski, E., Leone, D., Garratt, A. N., Birchmeier, C., & Suter, U. (2006). ErbB2 signalling in Schwann cells is mostly dispensable for maintenance of myelinated peripheral nerves and proliferation of adult Schwann cells after injury. Journal of Neuroscience, 26, 2124–2131.
Birchmeier, C., & Nave, K.-A. (2008). Neuregulin-1, a key axonal signal that drives Schwann cell growth and differentiation. Glia, 56, 1491–1497.
Boerboom, A., Dion, V., Chariot, A., & Franzen, R. (2017). Molecular mechanisms involved in Schwann cell plasticity. Frontiers in Molecular Neuroscience, 10, 38.
Britsch, S., Li, L., Kirchhoff, S., Theuring, F., Brinkmann, V., Birchmeier, C., & Riethmacher, D. (1998). The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system. Genes & Development, 12, 1825–1836.
Carroll, S. L., Miller, M. L., Frohnert, P. W., Kim, S. S., & Corbett, J. A. (1997). Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration. Journal of Neuroscience, 17, 1642–1659.
Cattin, A.-L., & Lloyd, A. C. (2016). The multicellular complexity of peripheral nerve regeneration. Current Opinion in Neurobiology, 39, 38–46.
Chaballe, L., Close, P., Sempels, M., Delstanche, S., Fanielle, J., Moons, L., Carmeliet, P., Schoenen, J., Chariot, A., & Franzen, R. (2011). Involvement of placental growth factor in Wallerian degeneration. Glia, 59, 379–396.
Creppe, C., Malinouskaya, L., Volvert, M.-L., Gillard, M., Close, P., Malaise, O., Laguesse, S., Cornez, I., Rahmouni, S., & Ormenese, S. (2009). Elongator controls the migration and differentiation of cortical neurons through acetylation of α-tubulin. Cell, 136, 551–564.
Evensen, N. A., Kuscu, C., Nguyen, H.-L., Zarrabi, K., Dufour, A., Kadam, P., Hu, Y., Pulkoski-Gross, A., Bahou, W. F., & Zucker, S. (2013). Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in cancer cell migration. Journal of the National Cancer Institute, 105, 1402–1416.
Fallon, K. B., Havlioglu, N., Hamilton, L. H., Cheng, T. P. H., & Carroll, S. L. (2004). Constitutive activation of the neuregulin-1/erbB signaling pathway promotes the proliferation of a human peripheral neuroepithelioma cell line. Journal of Neuro-Oncology, 66, 273–284.
Fledrich, R., Stassart, R. M., Klink, A., Rasch, L. M., Prukop, T., Haag, L., Czesnik, D., Kungl, T., Abdelaal, T. A. M., Keric, N., Stadelmann, C., Bruck, W., Nave, K.-A., & Sereda, M. W. (2014). Soluble neuregulin-1 modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A. Nature Medicine, 20, 1055–1061.
Frohnert, P. W., Stonecypher, M. S., & Carroll, S. L. (2003). Constitutive activation of the neuregulin-1/ErbB receptor signaling pathway is essential for the proliferation of a neoplastic Schwann cell line. Glia, 43, 104–118.
Gao, X., Daugherty, R. L., & Tourtellotte, W. G. (2007). Regulation of low affinity neurotrophin receptor (p75NTR) by early growth response (Egr) transcriptional regulators. Molecular and Cellular Neuroscience, 36, 501–514.
Garratt, A. N., Britsch, S., & Birchmeier, C. (2000). Neuregulin, a factor with many functions in the life of a Schwann cell. Bioessays, 22, 987–996.
Grossmann, K. S., Wende, H., Paul, F. E., Cheret, C., Garratt, A. N., Zurborg, S., Feinberg, K., Besser, D., Schulz, H., Peles, E., Selbach, M., Birchmeier, W., & Birchmeier, C. (2009). The tyrosine phosphatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development. Proceedings of the National Academy of Sciences of the United States of America, 106, 16704–16709.
Guertin, A. D., Zhang, D. P., Mak, K. S., Alberta, J. A., & Kim, H. A. (2005). Microanatomy of axon/glial signaling during Wallerian degeneration. Journal of Neuroscience, 25, 3478–3487.
Harrisingh, M. C., Perez-Nadales, E., Parkinson, D. B., Malcolm, D. S., Mudge, A. W., & Lloyd, A. C. (2004). The Ras/Raf/ERK signaling pathway drives Schwann cell dedifferentiation. embo J, 23, 3061–3071.
He, Y., Kim, J. Y., Dupree, J., Tewari, A., Melendez-Vasquez, C., Svaren, J., & Casaccia, P. (2010). Yy1 as a molecular link between neuregulin and transcriptional modulation of peripheral myelination. Nature Neuroscience, 13, 1472–1480.
Inserra, M. M., Bloch, D. A., & Terris, D. J. (1998). Functional indices for sciatic, peroneal, and posterior tibial nerve lesions in the mouse. Microsurgery, 18, 119–124.
Jessen, K. R., & Mirsky, R. (2005). The origin and development of glial cells in peripheral nerves. Nature Reviews Neuroscience, 6, 671–682.
Jessen, K. R., & Mirsky, R. (2016). The repair Schwann cell and its function in regenerating nerves. The Journal of Physiology, 594, 3521–3531.
Ji, Y., Shen, M., Wang, X., Zhang, S., Yu, S., Chen, G., Gu, X., & Ding, F. (2012). Comparative proteomic analysis of primary Schwann cells and a spontaneously immortalized Schwann cell line RSC 96, a comprehensive overview with a focus on cell adhesion and migration related proteins. Journal of Proteome Research, 11, 3186–3198.
Kim, H. A., Mindos, T., & Parkinson, D. B. (2013). Plastic fantastic, Schwann cells and repair of the peripheral nervous system. Stem Cells Translational Medicine, 2, 553–557.
Kuscu, C., Evensen, N., Kim, D., Hu, Y.-J., Zucker, S., & Cao, J. (2012). Transcriptional and epigenetic regulation of KIAA1199 gene expression in human breast cancer. PLoS One, 7, e44661-
Kwon, Y. K., Bhattacharyya, A., Alberta, J. A., Giannobile, W. V., Cheon, K., Stiles, C. D., & Pomeroy, S. L. (1997). Activation of ErbB2 during wallerian degeneration of sciatic nerve. Journal of Neuroscience, 17, 8293–8299.
Li, H., Wigley, C., & Hall, S. M. (1998). Chronically denervated rat Schwann cells respond to GGF in vitro. Glia, 24, 290–303.
Mahanthappa, N. K., Anton, E. S., & Matthew, W. D. (1996). Glial growth factor 2, a soluble neuregulin, directly increases Schwann cell motility and indirectly promotes neurite outgrowth. Journal of Neuroscience, 16, 4673–4683.
Matsuzaki, S., Tanaka, F., Mimori, K., Tahara, K., Inoue, H., & Mori, M. (2009). Clinicopathologic significance of KIAA1199 overexpression in human gastric cancer. Annals of Surgical Oncology, 16, 2042–2051.
Mercier, G., Turque, N., & Schumacher, M. (2001). Rapid effects of triiodothyronine on immediate-early gene expression in Schwann cells. Glia, 35, 81–89.
Nagashima, T., Shimodaira, H., Ide, K., Nakakuki, T., Tani, Y., Takahashi, K., Yumoto, N., & Hatakeyama, M. (2007). Quantitative transcriptional control of ErbB receptor signaling undergoes graded to biphasic response for cell differentiation. The Journal of Biological Chemistry, 282, 4045–4056.
Napoli, I., Noon, L. A., Ribeiro, S., Kerai, A. P., Parrinello, S., Rosenberg, L. H., Collins, M. J., Harrisingh, M. C., White, I. J., & Woodhoo, A. (2012). A central role for the ERK-signaling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo. Neuron, 73, 729–742.
Newbern, J., & Birchmeier, C. (2010). Nrg1/ErbB signaling networks in Schwann cell development and myelination. Seminars in Cell and Developmental Biology, 21, 922–928.
Newbern, J. M., Li, X., Shoemaker, S. E., Zhou, J., Zhong, J., Wu, Y., Bonder, D., Hollenback, S., Coppola, G., Geschwind, D. H., Landreth, G. E., & Snider, W. D. (2011). Specific functions for ERK/MAPK signaling during PNS development. Neuron, 69, 91–105.
Newbern, J. M., & Snider, W. D. (2012). Bers-ERK Schwann cells coordinate nerve regeneration. Neuron, 73, 623–626.
Noseda, R., Belin, S., Piguet, F., Vaccari, I., Scarlino, S., Brambilla, P., Martinelli Boneschi, F., Feltri, M. L., Wrabetz, L., Quattrini, A., Feinstein, E., Huganir, R. L., & Bolino, A. (2013). DDIT4/REDD1/RTP801 is a novel negative regulator of Schwann cell myelination. Journal of Neuroscience, 33, 15295–15305.
Parkinson, D. B., Bhaskaran, A., Arthur-Farraj, P., Noon, L. A., Woodhoo, A., Lloyd, A. C., Feltri, M. L., Wrabetz, L., Behrens, A., Mirsky, R., & Jessen, K. R. (2008). c-Jun is a negative regulator of myelination. The Journal of Cell Biology, 181, 625–637.
Ronchi, G., Haastert-Talini, K., Fornasari, B. E., Perroteau, I., Geuna, S., & Gambarotta, G. (2016). The Neuregulin1/ErbB system is selectively regulated during peripheral nerve degeneration and regeneration. European Journal of Neuroscience, 43, 351–364.
Sheu, J. Y., Kulhanek, D. J., & Eckenstein, F. P. (2000). Differential patterns of ERK and STAT3 phosphorylation after sciatic nerve transection in the rat. Experimental Neurology, 166, 392–402.
Shostak, K., Zhang, X., Hubert, P., Göktuna, S. I., Jiang, Z., Klevernic, I., Hildebrand, J., Roncarati, P., Hennuy, B., Ladang, A., Somja, J., Gothot, A., Close, P., Delvenne, P., & Chariot, A. (2014). NF-κB-induced KIAA1199 promotes survival through EGFR signaling. Nature Communications, 5, 5232-
Siconolfi, L. B., & Seeds, N. W. (2001). Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush. Journal of Neuroscience, 21, 4348–4355.
Syed, N., Reddy, K., Yang, D. P., Taveggia, C., Salzer, J. L., Maurel, P., & Kim, H. A. (2010). Soluble neuregulin-1 has bifunctional, concentration-dependent effects on Schwann cell myelination. Journal of Neuroscience, 30, 6122–6131.
Tapinos, N., Ohnishi, M., & Rambukkana, A. (2006). ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli. Nature Medicine, 12, 961–966.
Terashima, M., Fujita, Y., Togashi, Y., Sakai, K., De Velasco, M. A., Tomida, S., & Nishio, K. (2014). KIAA1199 interacts with glycogen phosphorylase kinase beta-subunit (PHKB) to promote glycogen breakdown and cancer cell survival. Oncotarget, 5, 7040–7050.
Tiwari, A., Schneider, M., Fiorino, A., Haider, R., Okoniewski, M. J., Roschitzki, B., Uzozie, A., Menigatti, M., Jiricny, J., & Marra, G. (2013). Early insights into the function of KIAA1199, a markedly overexpressed protein in human colorectal tumors. PLoS One, 8, e69473-
Topilko, P., Levi, G., Merlo, G., Mantero, S., Desmarquet, C., Mancardi, G., & Charnay, P. (1997). Differential regulation of the zinc finger genes Krox-20 and Krox-24 (Egr-1) suggests antagonistic roles in Schwann cells. Journal of Neuroscience Research, 50, 702–712.
Vogelaar, C. F., Vrinten, D. H., Hoekman, M. F. M., Brakkee, J. H., Burbach, J. P. H., & Hamers, F. P. T. (2004). Sciatic nerve regeneration in mice and rats: recovery of sensory innervation is followed by a slowly retreating neuropathic pain-like syndrome. Brain Research, 1027, 67–72.
Woldeyesus, M. T., Britsch, S., Riethmacher, D., Xu, L., Sonnenberg-Riethmacher, E., Abou-Rebyeh, F., Harvey, R., Caroni, P., & Birchmeier, C. (1999). Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development. Genes & Development, 13, 2538–2548.
Woodhoo, A., Alonso, M. B. D., Droggiti, A., Turmaine, M., D'Antonio, M., Parkinson, D. B., Wilton, D. K., Al-Shawi, R., Simons, P., Shen, J., Guillemot, F., Radtke, F., Meijer, D., Feltri, M. L., Wrabetz, L., Mirsky, R., & Jessen, K. R. (2009). Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity. Nature Neuroscience, 12, 839–847.
Yoshida, H., Nagaoka, A., Kusaka-Kikushima, A., Tobiishi, M., Kawabata, K., Sayo, T., Sakai, S., Sugiyama, Y., Enomoto, H., & Okada, Y. (2013). KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization. Proceedings of the National Academy of Sciences United States of America, 110, 5612–5617.
Yoshino, Y., Ishisaka, M., Tsuruma, K., Shimazawa, M., Yoshida, H., Inoue, S., Shimoda, M., Okada, Y., & Hara, H. (2017). Distribution and function of hyaluronan binding protein involved in hyaluronan depolymerization (HYBID, KIAA1199) in the mouse central nervous system. Neuroscience, 347, 1–10.