Abstract
The growth-associated protein B-50, also termed GAP-43, is a membrane-bound phosphoprotein that is expressed in neurons. It is particularly abundant during periods of axonal outgrowth in development and regeneration of the central and peripheral nervous system. In this paper we study the expression of B-50 in inflammatory and dystrophic myopathies. To investigate the state of regeneration, N-CAM and vimentin serial sections were performed, because N-CAM and cytoskeletal protein vimentin are excellent markers for regenerating muscle. Light-microscopic evaluation showed that muscle fiber regeneration in myopathies corresponds closely to B-50 immunoreactivity in satellite cells, myoblasts, myotubes and small regenerating myocytes in cytoplasmatic distribution. In normal muscle and in biopsies of neurogenic muscular atrophy, however, no light-microscopically demonstrable B-50 staining was found. B-50 in muscles apparently plays a role in the growth morphology of regenerating myocytes, and the phosphoprotein B-50 can no longer be regarded as a neuron-specific molecule.
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References
Aloyo VJ, Zwiers H, Gispen WH (1983) Phosphorylation of B-50 protein by calcium-activated, phospholipid-dependent protein kinase and B-50 kinase. J Neurochem 41:649–653
Arahata K, Engel A (1984) Monoclonal antibody analysis of mononuclear cells in myopathies. I. Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. Ann Neurol 16:193–208
Banker BQ, Hohlfeld R, Engel AG (1994) The polymyositis and dermatomyositis syndromes. In: (eds) Myology. McGraw-Hill, New York, pp 1335–1384
Bohan A, Peter JB (1975) Polymyositis and dermatomyositis. N Engl J Med 292:344–347, 403–407
Bornemann A, Schmalbruch H (1992) Desmin and vimentin in regenerating muscles. Muscle Nerve 15:14–20
Cashman NR, Covault J, Wollman RL, Sanes JR (1987) Neural cell adhesion molecule in normal, denervated, and myopathic human muscle. Ann Neurol 21:481–489
Covault J, Merlie JP, Gordis C, Sanes JR (1986) Molecular forms of N-CAM and its mRNA in developing and denervated skeletal muscle. J Cell Biol 102:731–739
DeGraan PNE, Oestreicher AB, DeWit M, Kroef M, Schrama LH, Gispen WH (1990) Evidence for the binding of calmodulin to endogenous B-50 (GAP43) in native synaptosomal plasma membranes. J Neurochem 55:2139–2141
Doriguzzi C, Mongini T, Palmucci L, Schiffer D (1983) A new method for myofibrillar Ca++-ATPase reaction based on the use of metachromatic dyes: its advantage in muscle fiber typing. Histochemistry 79:289–294
Engel AG, Yamamoto M, Fischbeck KH (1994) Dystrophinopathies. In: (eds) Myology. McGraw-Hill, New York, pp 1130–1187
Gordon-Weeks PR (1989) GAP43 — what does it do in the growth cone? Trends Neurosci 12:363–365
Henderson JR (1967) The use of silver for intensifying sulfide deposits in the cholinesterase technique. Stain Technol 42:101–102
Hesselmans LFGM, Jennekens FGI, Van denOr CJM, Oestreicher AB, Veldman H, Gispen WH (1989) A light and electron microscopical study of B-50 (GAP43) in human intramuscular nerve and neuromuscular junctions during development. J Neurol Sci 89:301–311
Heuß D, Engelhardt A, Lochmüller H, Göbel H, Neundörfer B (1994) Expression of GAP43 and NCAM in congenital fiber type disproportion with interstitial myositis. Virchows Arch [A] 421:578–582
Hohlfeld R (1989) Induction of HLA-DR expression on human myoblast with interferon-gamma. Am J Pathol 136:503–508
Illa J. Leon-Monzon M, Dalakas MC (1992) Regeneration and denervated human muscle fibers and satellite cells express neural cell adhesion molecule recognized by monoclonal antibodies to natural killer cells. Ann Neurol 31:46–52
Kaminska AM, Fidzianska A (1989) The response of rat skeletal muscle to injury as related to the stage of maturation and innervation. In: Fardeau M, Frezal J, Henderson CE (eds) Spinal muscular atrophies. Association Française contre les Myopathies (AFM), Ile des Embiez, France, pp 55–58
Karpati G, Carpenter S (1993) Pathology of the inflammatory myopathies. In: Mastaglia FL (ed) Clinical neurology, vol 2/3. Baillière Tindall, London, pp 527–556
Knyihár-Csillik E, Csillik B, Oestreicher AB (1992) Light and electron microscopic localization of B-50 (GAP43) in the rat spinal cord during transganglionic degenerative atrophy and regeneration. J Neurosci Res 32:93–109
Koelle GB, Friedenswald JS (1949) A histochemical method for localizing cholinesterase activity. Proc Soc Exp Biol Med 70:617–622
Lanier LL, Testi R, Brindl J, Phillips JH (1988) Identity of Leu19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med 169:2233–2238
Lewis PR (1961) The effect of varying the conditions in the Koelle technique. Bibl Anat 2:11–20
Meiri KF, Pfenninger KH, Willard MV (1986) Growth-associated protein GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci USA 83:3537–3541
Moore SE, Thompson J, Kirkness V, Dickson JG, Walsh FS (1987) Skeletal muscle neural cell adhesion molecule (N-CAM): changes in protein and mRNA species during myogenesis of muscle cell lines. J Cell Biol 105:1377–1386
Moos DJ, Fernyhough P, Chapman K, Baizer L, Bray D, Allsopp T (1990) Chicken growth-associated protein GAP-43 is tightly bound to the actin-rich neuronal membrane skeleton. J Neurochem 54:729–736
Müller-Felber W, Kullmer K, Fischer P, Reimers CD, Wagner S, Harland U, Schmidt-Achert M, Pongratz D (1993) Fiber type specific expression of Leu19-antigen and N-CAM in skeletal muscle in various stages after experimental denervation. Virchows Arch [A] 422:277–283
Nielander HV, Schrama LH, VanRozen AJ, Kasperaitis M, Oestreicher AB, DeGraan PNE, Gispen WH, Schorman P (1987) Primary structure of neuron-specific phosphoprotein B-50 is identical to growth-associated protein GAP43. Neurosci Res Commun 1:103–173
Schubert W, Zimmermann K, Cramer M, Starzinsky-Powitz A (1989) Lymphocyte antigen Leu-19 as a molecular marker of regeneration in human skeletal muscle. Proc Natl Acad Sci USA, 86:307–311
Skene JHP, Willard M (1981) Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous system. J Cell Biol 89:96–103
Skene JHP, Jacobson RD, Snipes JG, McGuire CB, Norden JJ, Freeman JA (1986) A protein induced during nerve growth (GAP43) is a major component of growth cone membranes. Science 233:783–786
Stocker KM, Baizer L, Ciment G (1992) Transient expression of GAP-43 in nonneuronal cells of the embryonic chicken limb. Dev Biol 149:406–414
Tetzlaff W, Zwiers H, Lederis K, Cassar L, Bisby MA (1989) Axonal transport and localization of B-50/GAP43-like immunoreactivity in regenerating sciatic and facial nerves of the rat. J Neurosci 9:1303–1313
VanLookeren Campagne M, Oestreicher AB, VanBergen EN, Henegouwen PMP, Gispen WH (1989) Ultrastructural immunocytochemical localization of B-50/GAP43, a protein kinase C substrate, in isolated presynaptic nerve terminals and nerve growth cones. J Neurocytol 18:479–489
Verhaagen J, Oestreicher AB, Edwards PM, Veldman H, Jennekens FG, Gispen WH (1988) Light- and electron-microscopical study of phosphoprotein B-50 following denervation and reinnervation of the rat soleus muscle. J Neurosci 8:1759–1766
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Heuβ, D., Engelhardt, A., Göbel, H. et al. Light-microscopic study of phosphoprotein B-50 in myopathies. Vichows Archiv A Pathol Anat 426, 69–76 (1995). https://doi.org/10.1007/BF00194700
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DOI: https://doi.org/10.1007/BF00194700