Skip to main content
Log in

Regulation of the p75 Neurotrophin Receptor in a Rat Myogenic Cell Line (L6)

  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Abstract

Neurotrophins are expressed in muscle cells both during development and postnatally. Furthermore, during development muscle cells express high levels of the common p75 neurotrophin receptor, which binds all neurotrophins. Only fragmentary and controversial data are available regarding the responsiveness of muscle cells to neurotrophins and the importance of low-affinity p75 receptor in muscle development. The present study investigates in vitro the immunocytochemical expression of p75 in a rat myogenic cell line (L6) at various time points and in response to different coating substrates as a first step in elucidating the regulation of p75 in muscle. We found that in L6 myoblasts, p75 is expressed only at very early stages of maturation and its levels of expression are regulated by the nature of the coating substrates. p75 expression decreases in cells growing on substrates more suitable for myoblast fusion into myotubes. Time course analysis indicates a reverse correlation between myoblast fusion into myotubes and the levels of p75 expression. Myotubes were always p75 negative. Substrates not suitable for the fusion process induced a prolonged presence of p75 in myoblasts with an increase of their apoptosis. We conclude that expression of p75, at least in this in vitro condition, is regulated by the stages of myoblast differentiation and the nature of the coating substrates. According to the observed time- and substrate-related evidences, future studies should investigate in vivo both the regulation of p75 in the myoblast fusion and the effects and the importance of neurotrophins binding during myoblast differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References cited

  • Acheson A, Lindsay RM (1996) Non target-derived roles of the neurotrophins. Philos Trans R Soc Lond (Biol) 351: 417-422.

    Google Scholar 

  • Autieri MV, Yue TL, Ferstein GZ, Ohlstein E (1995) Antisense oligonucleotides to the p65 subunit of NF-κBinhibit human vascular smooth muscle cell adherence and proliferation and prevent neointima formation in rat carotid arteries. Biochem Biophys Res Commun 213: 827-836.

    Google Scholar 

  • Baeuerle PA, Henkel T (1994) Function and activation of NF-κB in the immune system. Annu Rev Immunol 12: 141-179.

    Google Scholar 

  • Barbacid M (1995) Structural and functional properties of the Trk family of neurotrophin receptors. Ann NY Acad Sci 766: 442-458.

    Google Scholar 

  • Baron P, Scarpini E, Meola G, Santilli I, Conti G, Pleasure D, Scarlato G (1994) Expression of the low-affinity NGF receptor during human muscle development, regeneration, and in tissue culture. Muscle Nerve 17: 276-284.

    Google Scholar 

  • Barrett GL, Bartlett PF (1994) The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development. Proc Natl Acad Sci USA 91: 6501-6505.

    Google Scholar 

  • Barrett GL, Georgiou A (1996) The low-affinity nerve growth factor receptor p75NGFR mediates death of PC12 cells after nerve growth factor withdrawal. J Neurosci Res 45: 117-128.

    Google Scholar 

  • Bellas RE, Lee JS, Sonenshein GE (1995) Expression of a constitutive NF-κB like activity is essential for proliferation of cultured bovine vascular smooth muscle cells. J Clin Invest 96: 2521-2527.

    Google Scholar 

  • Brodie C, Sampson SR (1987) Nerve growth factor supports growth of rat skeletal myotubes in culture. Brain Res 435: 393-397.

    Google Scholar 

  • Brodie C, Sampson SR (1990) Nerve growth factor and fibroblast growth factor influence post-fusion expression of Na-channels in cultured rat skeletal muscle. J Cell Physiol 144: 492-497.

    Google Scholar 

  • Carter BD, Kaltschmidt C, Kaltschmidt B, Offenhäuser N, Böhm-Matthaei R, Baeuerle PA, Barde Y-A (1996) Selective activation of NF-¨oB by nerve growth factor through the neurotrophin receptor p75. Science 272: 542-545.

    Google Scholar 

  • Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV (1996) Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 383: 716-719.

    Google Scholar 

  • Chao MV, Hempstead BL (1995) p75 and Trk: A two-receptor system. Trends Neurosci 18: 321-326.

    Google Scholar 

  • Davies AM, Wright EM (1995) Neurotrophic factors: Neurotrophin autocrine loops. Curr Biol 5: 723-726.

    Google Scholar 

  • Del Valle ME, Calzada B, Suarez-Garnacho S, Vega JA (1992) Nerve growth factor receptor (NGFr) immunoreactivity in skeletal muscles of the rat. Cell Mol Biol 38: 443-448.

    Google Scholar 

  • Delaporte C, Dautreaux B (1987) Differentiation of human muscle cells in the presence of neuronal conditioned medium (NCM), nerve growth factor (NGF) and spinal cord cells (SC). Adv Exp Med Biol 209: 15-17.

    Google Scholar 

  • Ernfors P, Hallböök, F, Ebendal T, Shooter EM, Radeke MJ, Misko TP, Persson H (1988) Developmental and regional expression of β nerve growth factor receptor mRNA in chick and rat. Neuron 1: 983-996.

    Google Scholar 

  • Frade JM, Rodríguez-Tébar A, Barde Y-A (1996) Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 383: 166-168.

    Google Scholar 

  • Funakoshi H, Belluardo N, Arenas E, Yamamoto Y, Casabona A, Persson H, Ibáñez CF (1995) Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. Science 268: 1495-1499.

    Google Scholar 

  • Funakoshi H, Frisén, J, Barbany G, Timmusk T, Zachrisson O, Verge VMK, Persson H (1993) Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol 123: 455-465.

    Google Scholar 

  • Griesbeck O, Parsadanian AS, Sendtner M, Thoenen H (1995) Expression of neurotrophins in skeletal muscle: Quantitative comparison and significance for motoneuron survival and maintenance of function. J Neurosci Res 42: 21-33.

    Google Scholar 

  • Henderson CE, Camu W, Mettling C, Gouin A, Poulsen K, Karihaloo M, Rullamas J, Evans T, McMahon SB, Armanini MP, Berkemeier L, Phillips HS, Rosenthal A (1993) Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature 363: 266-270.

    Google Scholar 

  • Ip NY, Yancopoulos GD (1994) Neurotrophic factors and their receptors. Ann Neurol 35(Suppl): S13-S16.

    Google Scholar 

  • Ip NY, Yancopoulos GD (1996) The neurotrophins and CNTF: Two families of collaborative neurotrophic factors. Annu Rev Neurosci 19: 491-515.

    Google Scholar 

  • Koliatsos VE, Cayouette MH, Berkemeier LR, Clatterbuck RE, Price DL, Rosenthal A (1994) Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons. Proc Natl Acad Sci USA 91: 3304-3308.

    Google Scholar 

  • Koliatsos VE, Clatterbuck RE, Winslow JW, Cayouette MH, Price DL (1993) Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10: 359-367.

    Google Scholar 

  • Lewin GR (1996) Neurotrophins and the specification of neuronal phenotype. Philos Trans R Soc Lond (Biol) 351: 405-411.

    Google Scholar 

  • Lewin GR, Barde Y-A (1996) Physiology of the neurotrophins. Annu Rev Neurosci 19: 289-317.

    Google Scholar 

  • Lomen-Hoerth C, Shooter EM (1995) Widespread neurotrophin receptor expression in the immune system and other nonneuronal rat tissues. J Neurochem 64: 1780-1789.

    Google Scholar 

  • Nicoletti I, Migliorati G, Pagliacci C, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139: 271-279.

    Google Scholar 

  • Qwarnstrom EE, Ostberg CO, Turk GL, Richardson CA, Bomsztyk K (1994) Fibronectin attachment activates the NF-κB p50/p65 heterodimer in fibroblasts and smooth muscle cells. J Biol Chem 269: 30765-30768.

    Google Scholar 

  • Rabizadeh S, Bredesen DE (1994) Is p75NGFR involved in developmental neural cell death. Dev Neurosci 16: 207-211.

    Google Scholar 

  • Rabizadeh S, Oh J, Zhong L, Yang J, Bitler CM, Butcher LL, Bredesen DE (1993) Induction of apoptosis by the low-affinity NGF receptor. Science 261: 345-348.

    Google Scholar 

  • Radeva V (1978) Effects of the nerve growth factor (NGF) on certain non-neuronal elements. Agressologie 19: 99-103.

    Google Scholar 

  • Rende M, Giambanco I, Buratta M, Tonali P (1995) Axotomy induces a different modulation of both low-affinity nerve growth factor receptor and choline acetyltransferase between adult rat spinal and brainstem motoneurons. J Comp Neurol 363: 249-263.

    Google Scholar 

  • Rende M, Hagg T, Manthorpe M, Varon S (1992) Nerve growth factor receptor immunoreactivity in neurons of the adult rat spinal cord and its modulation after peripheral nerve lesions. J Comp Neurol 319: 285-298.

    Google Scholar 

  • Rende M, Provenzano C, Tonali P (1993) Modulation of low-affinity nerve growth factor receptor in injured adult rat spinal cord motoneurons. J Comp Neurol 338: 560-574.

    Google Scholar 

  • Sanes JR (1987) Cell lineage and the origin of muscle fiber types. TINS 10: 219-221.

    Google Scholar 

  • Schecterson LC, Bothwell M (1992) Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons. Neuron 9: 449-463.

    Google Scholar 

  • Segal RA, Greenberg ME (1996) Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci 19: 463-489.

    Google Scholar 

  • Seidl K, Erck C, Buchberger A (1998) Evidence for participation of nerve growth factor and its low-affinity receptor (p75) in the regulation of the myogenic program. J Cell Physiol 176: 10-21.

    Google Scholar 

  • Shin WS, Hong YH, Peng HB, De Caterina R, Libby P, Liao JK (1996) Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma. The role of constitutive NF-κB activity. J Biol Chem 271: 11317-11324.

    Google Scholar 

  • Timmusk T, Belluardo N, Metsis M, Persson H (1993) Widespread and developmentally regulated expression of neurotrophin-4 mRNA in rat brain and peripheral tissues. Eur J Neurosci 5: 605-613.

    Google Scholar 

  • Van der Zee CEEM, Ross GM, Riopelle RJ, Hagg T (1996) Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice. Science 274: 1729-1732.

    Google Scholar 

  • Wheeler EF, Bothwell M (1992) Spatiotemporal patterns of expression of NGF and the low-affinity NGF receptor in rat embryos suggest functional roles in tissue morphogenesis and myogenesis. J Neurosci 12: 930-945.

    Google Scholar 

  • Wheeler EF, Gong H, Grimes R, Benoit D, Vasquez L (1998) The p75NTR and Trk receptors are expressed in reciprocal patterns in a wide variety of non-neural tissues during rat embryonic development, indicating independent receptor functions. J Comp Neurol 391: 407-428.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rende, M., Brizi, E., Sorci, G. et al. Regulation of the p75 Neurotrophin Receptor in a Rat Myogenic Cell Line (L6). Histochem J 31, 589–602 (1999). https://doi.org/10.1023/A:1003851024732

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1003851024732

Keywords

Navigation