Abstract
Ebp1, an ErbB3-binding protein, is the human homologue of the cell cycle-regulated mouse protein p38-2G4. Ebp1 was reported to inhibit the proliferation and induce the differentiation of human cancer cells. Its p48 isoform contributes to neuronal differentiation and growth factor specificity. However, the expression and role of Ebp1 in peripheral system lesions and repair are still unknown. Herein, we investigated the spatiotemporal pattern of Ebp1 expression following sciatic nerve crush. After crush, the level of Ebp1 protein was elevated gradually, peaked at day 5, and then declined to the normal at 4 weeks, which was similar to the expression of Oct-6. Furthermore, using double immunofluorescent staining, we found Ebp1 had a colocalization with S100 and Oct-6 in 5-day injured tissues. In vitro, we observed enhanced expression of Ebp1 during the process of cyclic adenosine monophosphate (cAMP)-induced Schwann cells differentiation. Interestingly, Ebp1-depleted SCs did not show significant morphologic change after the treatment of cAMP. Also, we observed a colocalization between Ebp1 and Cyclin D1 and that Ebp1-specific siRNA-transfected SCs had a decreased migration. Taken together, we speculated that Ebp1 was upregulated in the sciatic nerve after crush, which was involved in the differentiation and migration of Schwann cells.
Similar content being viewed by others
Abbreviations
- Ebp1:
-
ErbB3-binding protein 1
- SCs:
-
Schwann cells
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- PNS:
-
Peripheral nervous system
- CNS:
-
Central nervous system
- PNI:
-
Peripheral nerves injury
- SNC:
-
Sciatic nerve crush
- cAMP:
-
Cyclic adenosine monophosphate
- HRG:
-
Heregulin
- NRG1:
-
Neuregulin 1
- P0:
-
Myelin protein zero
References
Akassoglou K, Yu WM, Akpinar P, Strickland S (2002) Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation. Neuron 33(6):861–875
Arroyo EJ, Bermingham JR Jr, Rosenfeld MG, Scherer SS (1998) Promyelinating Schwann cells express Tst-1/SCIP/Oct-6. J Neurosci: Off J Soc Neurosci 18(19):7891–7902
Atanasoski S, Shumas S, Dickson C, Scherer SS, Suter U (2001) Differential cyclin D1 requirements of proliferating Schwann cells during development and after injury. Mol Cell Neurosci 18(6):581–592. doi:10.1006/mcne.2001.1055
Chen ZL, Yu WM, Strickland S (2007) Peripheral regeneration. Annu Rev Neurosci 30:209–233. doi:10.1146/annurev.neuro.30.051606.094337
Eser F, Aktekin LA, Bodur H, Atan C (2009) Etiological factors of traumatic peripheral nerve injuries. Neurol India 57(4):434–437. doi:10.4103/0028-3886.55614
Fawcett JW, Keynes RJ (1990) Peripheral nerve regeneration. Annu Rev Neurosci 13:43–60. doi:10.1146/annurev.ne.13.030190.000355
Figeac N, Serralbo O, Marcelle C, Zammit PS (2014) ErbB3 binding protein-1 (Ebp1) controls proliferation and myogenic differentiation of muscle stem cells. Dev Biol 386(1):135–151. doi:10.1016/j.ydbio.2013.11.017
Goldberg JL, Barres BA (2000) The relationship between neuronal survival and regeneration. Annu Rev Neurosci 23:579–612. doi:10.1146/annurev.neuro.23.1.579
Horvath BM, Magyar Z, Zhang Y, Hamburger AW, Bako L, Visser RG, Bachem CW, Bogre L (2006) EBP1 regulates organ size through cell growth and proliferation in plants. EMBO J 25(20):4909–4920. doi:10.1038/sj.emboj.7601362
Hunter T, Pines J (1994) Cyclins and cancer. II: cyclin D and CDK inhibitors come of age. Cell 79(4):573–582
Ide C (1996) Peripheral nerve regeneration. Neurosci Res 25(2):101–121
Jeselsohn R, Brown NE, Arendt L, Klebba I, Hu MG, Kuperwasser C, Hinds PW (2010) Cyclin D1 kinase activity is required for the self-renewal of mammary stem and progenitor cells that are targets of MMTV-ErbB2 tumorigenesis. Cancer Cell 17(1):65–76. doi:10.1016/j.ccr.2009.11.024
Jessen KR, Mirsky R (2005) The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci 6(9):671–682. doi:10.1038/nrn1746
Konigsmark BW, Murphy EA (1970) Neuronal populations in the human brain. Nature 228:1335–1336
Kwon IS, Ahn JY (2011) p48 Ebp1 acts as a downstream mediator of Trk signaling in neurons, contributing neuronal differentiation. Neurochem Int 58(2):215–223. doi:10.1016/j.neuint.2010.12.001
Lange C, Huttner WB, Calegari F (2009) Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell 5(3):320–331. doi:10.1016/j.stem.2009.05.026
Lessor TJ, Yoo JY, Xia X, Woodford N, Hamburger AW (2000) Ectopic expression of the ErbB-3 binding protein ebp1 inhibits growth and induces differentiation of human breast cancer cell lines. J Cell Physiol 183(3):321–329. doi:10.1002/(SICI)1097-4652(200006)183:3<321::AID-JCP4>3.0.CO;2-O
Li Z, Jiao X, Wang C, Ju X, Lu Y, Yuan L, Lisanti MP, Katiyar S, Pestell RG (2006a) Cyclin D1 induction of cellular migration requires p27(KIP1). Cancer Res 66(20):9986–9994. doi:10.1158/0008-5472.CAN-06-1596
Li Z, Wang C, Jiao X, Lu Y, Fu M, Quong AA, Dye C, Yang J, Dai M, Ju X, Zhang X, Li A, Burbelo P, Stanley ER, Pestell RG (2006b) Cyclin D1 regulates cellular migration through the inhibition of thrombospondin 1 and ROCK signaling. Mol Cell Biol 26(11):4240–4256. doi:10.1128/MCB.02124-05
Li H, Yang H, Liu Y, Huan W, Zhang S, Wu G, Lu Q, Wang Q, Wang Y (2011) The cyclin-dependent kinase inhibitor p27(Kip1) is a positive regulator of Schwann cell differentiation in vitro. J Mol Neurosci: MN 45(2):277–283. doi:10.1007/s12031-011-9518-2
Liu Z, Ahn JY, Liu X, Ye K (2006) Ebp1 isoforms distinctively regulate cell survival and differentiation. Proc Natl Acad Sci U S A 103(29):10917–10922. doi:10.1073/pnas.0602923103
Lyons DA, Pogoda HM, Voas MG, Woods IG, Diamond B, Nix R, Arana N, Jacobs J, Talbot WS (2005) erbb3 and erbb2 are essential for schwann cell migration and myelination in zebrafish. Curr Biol: CB 15(6):513–524. doi:10.1016/j.cub.2005.02.030
Makwana M, Raivich G (2005) Molecular mechanisms in successful peripheral regeneration. FEBS J 272(11):2628–2638. doi:10.1111/j.1742-4658.2005.04699.x
Martyn CN, Hughes RA (1997) Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry 62(4):310–318
Massague J (2004) G1 cell-cycle control and cancer. Nature 432(7015):298–306. doi:10.1038/nature03094
Morgan DO (1995) Principles of CDK regulation. Nature 374(6518):131–134. doi:10.1038/374131a0
Neumeister P, Pixley FJ, Xiong Y, Xie H, Wu K, Ashton A, Cammer M, Chan A, Symons M, Stanley ER, Pestell RG (2003) Cyclin D1 governs adhesion and motility of macrophages. Mol Biol Cell 14(5):2005–2015. doi:10.1091/mbc.02-07-0102
Newbern J, Birchmeier C (2010) Nrg1/ErbB signaling networks in Schwann cell development and myelination. Semin Cell Dev Biol 21(9):922–928. doi:10.1016/j.semcdb.2010.08.008
Pestell RG (2013) New roles of cyclin D1. Am J Pathol 183(1):3–9. doi:10.1016/j.ajpath.2013.03.001
Radomski N, Jost E (1995) Molecular cloning of a murine cDNA encoding a novel protein, p38-2G4, which varies with the cell cycle. Exp Cell Res 220(2):434–445. doi:10.1006/excr.1995.1335
Robinson LR (2000) Traumatic injury to peripheral nerves. Muscle Nerve 23(6):863–873
Scherer SS, Wang DY, Kuhn R, Lemke G, Wrabetz L, Kamholz J (1994) Axons regulate Schwann cell expression of the POU transcription factor SCIP. J Neurosci: Off J Soc Neurosci 14(4):1930–1942
Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512
Squatrito M, Mancino M, Donzelli M, Areces LB, Draetta GF (2004) EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes. Oncogene 23(25):4454–4465. doi:10.1038/sj.onc.1207579
Wan C, Jiang J, Mao H, Cao J, Wu X, Cui G (2013) Involvement of upregulated p53-induced death domain protein (PIDD) in neuronal apoptosis after rat traumatic brain injury. J Mol Neurosci: MN 51(3):695–702. doi:10.1007/s12031-013-0050-4
Wan C, Chen J, Hu B, Zou H, Li A, Guo A, Jiang J (2014) Downregulation of UBE2Q1 is associated with neuronal apoptosis in rat brain cortex following traumatic brain injury. J Neurosci Res 92(1):1–12. doi:10.1002/jnr.23305
Wang Y, Liu F, Mao F, Hang Q, Huang X, He S, Wang Y, Cheng C, Wang H, Xu G, Zhang T, Shen A (2013) Interaction with cyclin H/cyclin-dependent kinase 7 (CCNH/CDK7) stabilizes C-terminal binding protein 2 (CtBP2) and promotes cancer cell migration. J Biol Chem 288(13):9028–9034. doi:10.1074/jbc.M112.432005
Wu H, Liu Y, Zhou Y, Long L, Cheng X, Ji L, Weng H, Ding T, Yang J, Wei H, Li M, Huan W, Deng X, Wang Y (2013) Changes in the BAG1 expression of Schwann cells after sciatic nerve crush. J Mol Neurosci: MN 49(3):512–522. doi:10.1007/s12031-012-9910-6
Xia X, Lessor TJ, Zhang Y, Woodford N, Hamburger AW (2001) Analysis of the expression pattern of Ebp1, an ErbB-3-binding protein. Biochem Biophys Res Commun 289(1):240–244. doi:10.1006/bbrc.2001.5942
Yao L, Cao J, Sun H, Guo A, Li A, Ben Z, Zhang H, Wang X, Ding Z, Yang X (2014) FBP1 and p27kip1 expression after sciatic nerve injury: implications for Schwann cells proliferation and differentiation. J Cell Biochem 115(1):130–140
Yoo JY, Wang XW, Rishi AK, Lessor T, Xia XM, Gustafson TA, Hamburger AW (2000) Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin. Br J Cancer 82(3):683–690. doi:10.1054/bjoc.1999.0981
Zhang Y, Woodford N, Xia X, Hamburger AW (2003) Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases. Nucleic Acids Res 31(8):2168–2177
Zhang Y, Lu Y, Zhou H, Lee M, Liu Z, Hassel BA, Hamburger AW (2008) Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1) deficient mice. BMC Cell Biol 9:69. doi:10.1186/1471-2121-9-69
Zorick TS, Syroid DE, Arroyo E, Scherer SS, Lemke G (1996) The transcription factors SCIP and Krox-20 mark distinct stages and cell fates in Schwann cell differentiation. Mol Cell Neurosci 8(2–3):129–145. doi:10.1006/mcne.1996.0052
Acknowledgments
This work was supported by the National Natural Science Foundation of China (no. 31300902, no. 81171140).
Author information
Authors and Affiliations
Corresponding author
Additional information
Yang Liu and Yonghua Liu contributed equally to this work.
Rights and permissions
About this article
Cite this article
Liu, Y., Liu, Y., Cao, J. et al. Upregulated Expression of Ebp1 Contributes to Schwann Cell Differentiation and Migration After Sciatic Nerve Crush. J Mol Neurosci 54, 602–613 (2014). https://doi.org/10.1007/s12031-014-0331-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-014-0331-6