Abstract
Anterograde and retrograde transport within axons and dendrites of nerve cells represent an integral part of the nerve cell function and biochemistry. A few exogenous macromolecules with most different molecular weights and physico-chemical properties (Nerve Growth Factor, tetanus toxin, cholera toxin, various lectins, antibodies against dopamine-β-hydroxylase) have been shown to be taken up and transported with the retrograde axonal transport in exceedingly high amounts if compared to most other macromolecules. Specific binding to membrane receptors seems to be the prerequisite for this highly efficient retrograde transport. Upon arrival at the cell body tetanus toxin is able to leave the neuron and to migrate transsynaptically to presynaptic nerve terminals of second-order neurons.
For NGF, tetanus toxin and some neurotropic viruses retrograde axonal transport eventually followed by transsynaptic transport may be crucially involved in their mechanism of action. Indirect evidence suggests the existence of a variety of endogenous molecules carrying specific information from the target cell and the nerve terminal to the cell body and eventually transsynaptically into second- or third-order neurons.
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References
S. Ochs,Systems of Material Transport in Nerve Fibers (Axoplasmic Transport) Related to Nerve Function and Trophic Control, Ann. N.Y. Acad. Sci.228, 202–223 (1974).
J.W. Griffin, D.L. Price, D.B. Drachman andW.K. Engel,Axonal Transport to and from the Motor Nerve Ending, Ann. N.Y. Acad. Sci.274, 31–45 (1976).
P. Schubert, Y.W. Kreutzberg andH.O. Lux,Neuroplasmic Transport in Dendrites: Effect of Colchicine on Morphology and Physiology of Motoneurons in the Cat, Brain Res.47, 331–343 (1972).
M. Williard, W.M. Cowan andP.R. Vagelos,The Polypeptide Composition of Intra-Axonally Transported Proteins: Evidence for Four Transport Velocities, Proc. natl. Acad. Sci. 2183–2187 (1974).
L. Lubinska andS. Niemierko,Velocity and Intensity of Bidirectional Migration of AchE in Transsected Nerves, Brain Res.27, 329–342 (1971).
H. Thoenen, U. Otten andF. Oesch,Axoplasmic Transport of Enzymes Involved in the Synthesis of Noradernaline: Relationship Between the Rate of the Transport and Subcellular Distribution, Brain Res.62, 471–475 (1973).
K. Stöckel, M. Schwab andH. Thoenen,Comparison Between the Retrograde Axonal Transport of Nerve Growth Factor and Tetanus Toxin in Motor, Sensory and Adrenergic Neurons, Brain Res.99, 1–16 (1975).
J.L. Barker, J.H. Neale andH. Gainer,Rapidly Transported Proteins in Sensory, Motor and Sympathetic Nerves of the Isolated Frog Nervous System, Brain Res.105, 497–515 (1976).
J.O. Karlsson,Proteins of Axonal Transport: Investigation of Solubility Characteristics and Behaviour in gel Filtration, J. Neurochem.27, 1135–1143 (1976).
B. Droz, A. Rambourg andH.L. Koenig,The Smooth Endoplasmic Reticulum: Structure and Role in the Renewal of Axonal Membrane and Synaptic Vesicles by Fast Axonal Transport, Brain Res.93, 1–13 (1975).
J. Schonbach, Ch. Schonbach andM. Cuenod,Rapid Phase of Axoplasmic Flow and Synaptic Proteins: An Electron Microscopical Autoradiographic Study, J. Comp. Neurol.141, 485–498 (1971).
B. Droz, H. Koenig andL. Di Giamberardino,Axonal Migration of Protein and Glycoproteins to Nerve Endings: I. Radioautographic Analysis of Renewal of Protein in Nerve Endings of Chicken Ciliary Ganglion after Intracerebral Injection of H 3-lysine, Brain Res.60, 93–127 (1973).
G. Bennett, L. Di Giamberardino, H.L. Koenig andB. Droz,Axonal Migration of Protein and Glycoprotein to Nerve Endings. II. Radioautographic Analysis of the Renewal of Glycoproteins in Nerve Endings of Chicken Ciliary Ganglion after Intracerebral Injection of H 3-glucosamine, Brain Res.60, 129–146 (1973).
L. Di Giamberardino, G. Bennett, H.L. Koenig andB. Droz,Axonal Migration of Protein and Glycoprotein to Nerve Endings. III. Cell Fraction Analysis of Chicken Ciliary Ganglion after Intracerebral Injection of Labeled Precursors, of Proteins and Glycoproteins, Brain Res.60, 147–159 (1973).
P. Cancalon andL.M. Beidler,Differences in the Composition of the Polypeptides Deposited in the Axon and the Nerve Terminals by Fast Axonal Transport in the Garfish Olfactory Nerve, Brain Res.121, 215–227 (1977).
V. Krygier-Brevart, D.G. Weiss, E. Mehl, P. Schubert andG.W. Kreutzberg,Maintenance of Synaptic Membranes by the Fast Axonal Flow, Brain Res.77, 97–110 (1974).
M.A. Bisby,Orthograde and Retrograde Axonal Transport of Labeled Protein in Motoneurons, Exp. Neurol.50, 628–640 (1976).
M. Frizell, W.G. McLean J. Sjöstrand,Retrograde Axonal Transport of Rapidly Migrating Labelled Proteins and Glycoproteins in Regenerating Peripheral Nerves. J. Neurochem.27, 191–196 (1976).
I. Nagatsu, Y. Kondo, T. Kato andT. Nagatsu,Retrograde Axoplasmic Transport of Inactive Dopamine-β-hydroxylase in Sciatic Nerves, Brain Res.116, 277–285 (1976).
S. Brimijoin andL. Helland,Rapid Retrograde Transport of Dopamine-β-hydroxylase as Examined by the Stop-Flow Technique, Brain Res.102, 217–228 (1976).
K. Kristensson, Y. Olsson andJ. Sjostrand,Axonal Uptake and Retrograde Transport of Exogenous Protein in the Hypoglossal Nerve, Brain Res.32, 399–406 (1971).
H.J.W. Nauta, M.B. Pritz andR.J. Lasek,Afferents to the Rat Caudoputamen Studied with Horseradish Peroxidase. An Evaluation of a Retrograde Neuroanatomical Research Method, Brain Res.67, 219–238 (1974).
K. Stöckel, U. Paravicini andH. Thoenen,Specificity of the Retrograde Axonal Transport of Nerve Growth Factor, Brain Res.76, 413–421 (1974).
K. Stöckel, M. Schwab andH. Thoenen,Specificity of Retrograde Transport of Nerve Growth Factor (NGF) in Sensory Neurons: A Biochemical and Morphological Study, Brain Res.89, 1–14 (1975).
G. Erdmann, H. Wiegand andH.H. Wellhöner,Intraaxonal and Extraaxonal Transport of 125 I-Tetanus Toxin in Early Local Tetanus, Naunyn-Schmiedebergs Arch. Pharm.290, 357–373 (1975).
D.L. Price, J. Griffin, A. Young, K. Peck, andA. Stocks,Tetanus Toxin: Direct Evidence for Retrograde Intraaxonal Transport, Science188, 945–947 (1975).
K. Stöckel, M.E. Schwab, andH. Thoenen,Role of Gangliosides in the Uptake and Retrograde Axonal Transport of Cholera and Tetanus Toxin as Compared to Nerve Growth Factor and Wheat Germ Agglutinin, Brain Res. (in press).
M.G. Ziegler, J.A. Thomas andD.M. Jacobowitz,Retrograde Axonal Transport of Antibody to Dopamine-β-hydroxylase, Brain Res.104, 390–395 (1976).
M. Fillenz, C. Gagnon, K. Stöckel andH. Thoenen,Selective Uptake and Retrograde Axonal Transport of Dopamine-β-hydroxylase Antibodies in Peripheral Adrenergic Neurons. Brain Res.114, 293–303 (1976).
W.E. van Heyningen,Gangliosides as Membrane Receptors for Tetanus Toxin, Cholera Toxin and Serotonin, Nature249, 415–417 (1974).
M.E. Schwab,Ultrastructural Localization of a Nerve Growth Factor-Horseradish Peroxidase (NGF-HRP) Coupling Product after Retrograde Axonal Transport in Adrenergic Neurons, Brain Res.130, 190–196 (1977).
G.L. Nicolson,The Interactions of Lectins with Animal Cell Surfaces, Intern. Rev. Cytol.39, 89–190 (1974).
M.E. Schwab andH. Thoenen,Selective Binding Uptake and Retrograde Transport of Tetanus Toxin by Nerve Terminals in the Rat Iris, J. Cell. Biol. (submitted).
M.E. Schwab andH. Thoenen,Electron Microscopic Evidence for a Trans-synaptic Migration of Tetanus Toxin in Spinal Cord Motoneurons: An Autoradiographic and Morphometric Study, Brain Res.105, 213–227 (1976).
M.E. Schwab andH. Thoenen,Selective Trans-Synaptic Migration of Tetanus Toxin after Retrograde Axonal Transport in Peripheral Sympathetic Nerves: A Comparison with Nerve Growth Factor, Brain Res.122, 459–474 (1977).
U. Otten, M. Schwab, C. Gagnon andH. Thoenen,Selective Induction of Tyrosine Hydroxylase and Dopamine-β-hydroxylase by Nerve Growth Factor: Comparison Between Adrenal Medulla and Sympathetic Ganglia of Adult and Newborn Rats, Brain Res. (in press).
U. Paravicini, K. Stöckel andH. Thoenen,Biological Importance of Retrograde Axonal Transport of Nerve Growth Factor in Adrenergic Neurons, Brain Res.84, 279–291 (1975).
K. Fuxe, L. Olson andY. Zotterman,Dynamics of Degeneration and Growth in Neurons (Pergamon Press, Oxford, 1974).
E. Cooper, J. Diamond andC. Turner,The Effects of Nerve Section and of Colchicine Treatment on the Density of Mechanosensory Nerve Endings in Salamander skin, J. Physiol.264, 725–749 (1977).
B.G. Cragg,What is the Signal for Chromatolysis? Brain Res.23, 1–21 (1970).
I.A. Hendry andJ. Campbell,Morphometric Analysis of Rat Superior Cervical Ganglion after Axotomy and Nerve Growth Factor Treatment, J. Neurocytol.5, 351–360 (1976).
M.R. Matthews andV.H. Nelson,Detachment of Structurally Intact Nerve Endings from Chromatolytic Neurones of Rat Superior Cervical Ganglion during the Depression of Synaptic Transmission Induced by Post-Ganglionic Axotomy, J. Physiol.245, 91–135 (1975).
D. Purves,Functional and Structural Changes in Mammalian Sympathetic Neurones Following Interruption of their Axons, J. Physiol.252, 429–463 (1975).
D. Purves,Functional and Structural Changes in Mammalian Sympathetic Neurones Following Colchicine Application to Postganglionic Nerves, J. Physiol.259, 159–175 (1976).
B.E.H. Sumner,An Ultrastructural Study of Normal and Injured Hypoglossal Nuclei after Injection of Horseradish Peroxidase, Exp. Brain Res.23, 463–470 (1975).
L. Landmesser andG. Pilar,Fate of Ganglionic Synapses and Ganglion Cell Axons during Normal and Induced Cell Death, J. Cell Biol.68, 357–374 (1976).
W.M. Cowan,Anterograde and Retrograde Transneuronal Degeneration in the Central and Peripheral Nervous System, in:Contemporary Research Methods in Neuroanatomy (Eds. W.J.H. Nauta and S.O.E. Ebbesson; Springer, Berlin, 1970), pp. 217–251.
D.R. Curtis andW.C. De Groat,Tetanus Toxin and Spinal Inhibition, Brain Res.10, 208–212 (1968).
D.R. Curtis, D. Felix, C.J.A. Game andR.M. McCulloch,Tetanus Toxin and the Synaptic Release of GABA, Brain Res.51, 358–362 (1973).
R.H. Osborne andH.F. Bradford,Tetanus Toxin Inhibits Amino Acid Release from Nerve Endings in vitro, Nature New Biol.244, 157–158 (1973).
K. Blinzinger andA.P. Anzil,Neural Route of Infection in Viral Diseases of the Central Nervous System, Lancet7, 1374–1377 (1974).
M. Dolivo (personal communication).
K. Kristensson, B. Ghetti andH.M. Wisniewski,Study of the Propagation of Herpes Simplex Virus (Type 2) into the Brain after Intraocular Injection, Brain Res.69, 189–202 (1974).
F.A. Murphy, S.P. Baner, A.K. Harrison andW.C. Winn, Jr.,Comparative Pathogenesis of Rabies and Rabies-like Viruses. Viral Infection and Transmit from Inoculation Site to the Central Nervous Systems, Pathol. Invest.28, 361–376 (1973).
R.W. Price, B.J. Kath andA.L. Notkins,Latent Infection of the Peripheral ANS with Herpes Simplex Virus, Nature257, 686–688 (1975).
M.A. Walz, R.W. Price andA.L. Notkins,Latent Ganglionic Infection with Herpes Simplex Virus Types 1 and 2: Viral Reactivation in vivo after Neurectomy, Science184, 1185–1187 (1974).
B. Bizzini, K. Stöckel andM. Schwab,An Antigenic Polypeptide Fragment Isolated from Tetanus Toxin: Chemical Characterization, Binding to Gangliosides and Retrograde Axonal Transport in Various Neuron Systems, J. Neurochem.28, 529–542 (1977).
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Dedicated to K. Bucher on the occasion of his 65th birthday.
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Schwab, M.E., Thoenen, H. Retrograde axonal and transsynaptic transport of macromolecules: Physiological and pathophysiological importance. Agents and Actions 7, 361–368 (1977). https://doi.org/10.1007/BF01969569
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DOI: https://doi.org/10.1007/BF01969569