Abstract
Neurons require a large amount of intracellular transport. Cytoplasmic polypeptides and membrane-bounded organelles move from the perikaryon, down the length of the axon, and to the synaptic terminals. This movement occurs at distinct rates and is termed axonal transport. Axonal transport is divided into the slow transport of cytoplasmic proteins including glycolytic enzymes and cytoskeletal structures and the fast transport of membrane-bounded organelles along linear arrays of microtubules. The polypeptide compositions of the rate classes of axonal transport have been well characterized, but the underlying molecular mechanisms of this movement are less clear. Progress has been particularly slow toward understanding force-generation in slow transport, but recent developments have provided insight into the molecular motors involved in fast axonal transport. Recent advances in the cellular and molecular biology of one fast axonal transport motor, kinesin, have provided a clearer understanding of organelle movement along microtubules. The availability of cellular and molecular probes for kinesin and other putative axonal transport motors have led to a reevaluation of our understanding of intracellular motility.
Similar content being viewed by others
References
Allen R. D., Allen N. S., and Travis J. L. (1981) Video-enhanced contrast, differential interference contrast (AVEC-DIC) microscopy: A new method capable of analyzing microtubule-related motility in the reticulopodial network ofAllogromia laticollaris, Cell Motility 1, 291–302.
Allen R. D., Weiss D. G., Hayden, J. H., Brown D. T., Fujiwake H., and Simpson M. (1985) Gliding movement of and bidirectional transport along single native microtubules from squid axoplasm: evidence for an active role of microtubules in cytoplasmic transport.J. Cell Biol. 100, 1736–1752.
Bamburg J. R., Bray D., and Chapman K. (1986) Assembly of microtubules at the tip of growing axons.Nature 321, 778–790.
Black M. M. and Lasek R. J. (1979) Axonal transport of actin: Slow Component b is the principal source of actin for the axon.Brain Res. 171, 401–413.
Black M. M. and Lasek R. J. (1980) Slow components of axonal transport: two cytoskeletal networks.J. Cell Biol. 86, 616–623.
Bloom G. S. (1992) Motor proteins for cytoplasmic microtubules.Curr. Opinion in Cell Biology 4, 1–8.
Bloom G. S., Wagner M. C., Pfister K. K., and Brady S. T. (1988) Native structure and physical properties of bovine brain kinesin and identification of the ATP-binding subunit polypeptide.Biochemistry 27, 3409–3416.
Bloom G. S., Wagner M. C., Pfister K. K., Leopold P. L., and Brady S. T. (1989) Involvement of microtubules and kinesin in the fast axonal transport of membrane-bounded organelles, inDynein and Microtubules Dynamics, Warner F. D. and McIntosh J. R., eds., Alan R. Liss, New York, pp. 321–333.
Brady S. T. (1985a) A novel brain ATPase with properties expected for fast axonal transport.Nature 317, 73–75.
Brady S. T. (1985b) Axonal transport methods and applications, inGeneral Neurochemical Techniques, Boulton A.A. and Baker G. B., eds., Humana, Totowa, NJ, pp. 419–476.
Brady S. T. (1988) Cytotypic specializations of the neuronal cytoskeleton and cytomatrix: Implications for neuronal growth and regeneration, inCellular and Molecular Aspects of Neural Development and Regeneration, Haber B., Gorio A., de Vellis J., and Perez-Polo, J. R., eds., Springer-Verlag, New York, pp. 311–322.
Brady S. T. (1991) Molecular motors in the nervous system.Neuron 7, 1–20.
Brady S. T. (1992) Axonal dynamics and regeneration, inNeural Regeneration, Gorio A., eds., Raven, New York, in press.
Brady S. T. and Lasek R. J. (1981) Nerve-specific enolase and creatine phosphokinase in axonal transport: soluble proteins and the axoplasmic matrix.Cell 23, 515–523.
Brady S. T. and Lasek R. J. (1982a) Axonal transport: a cell-biological method for studying proteins that associate with the cytoskeleton.Methods Cell Biol. 25, 365–398.
Brady S. T. and Lasek R. J. (1982b) The slow components of axonal transport: movements, compositions and organization, inAxoplasmic Transport, Weiss D. G., ed., Springer-Verlag, Berlin, pp. 206–213.
Brady S. T., Lasek R. J., and Allen R. D. (1982) Fast axonal transport in extruded axoplasm from squid giant axon.Science 218, 1129–1131.
Brady S. T., Lasek R. J., and Allen R. D. (1985) Video microscopy of fast axonal transport in extruded axoplasm: a new model for study of molecular mechanisms.Cell Motility 5, 81–101.
Brady S. T., Lasek R. J., Allen R. D., Yin H. L., and Stossel T. P. (1984) Gelsolin inhibition of fast axonal transport indicates a requirement for actin microfilaments.Nature 310, 56–58.
Brady S. T., Tytell M., Heriot K., and Lasek R. J. (1981) Axonal transport of calmodulin: a physiological approach to identification of long-term associations between proteins.J. Cell Biol. 89, 607–614.
Breuer A. C., Allen R. D., and Lewis R. J. (1981) Rapid transport in neurites of “submicroscopic” structures: analysis by the new AVEC-DIC microscopy method.Neurology 31, 118a.
Burdwood W. O. (1964) Rapid particle movement in neurons.J. Cell Biol. 27, 115a.
Buster D., Lohka M., and Scholey J. M. (1990) Phosphorylation of sea urchin kinesin.J. Cell Biol. 111, 418a.
Chen M. S., Obar R. B., Schroeder C. C., Austin T. W., Poodry C. A., Wadsworth S. C., and Vallee R. B. (1991) Multiple forms of dynamin are encoded by shibire, a Drosophila gene involved in endocytosis.Nature 351, 583–586.
Cleveland D. W. and Hoffman P. N. (1991) Slow axonal transport models come full circle: Evidence that microtubule sliding mediates axonal elongation and tubulin transport.Cell 67, 453–456.
Cohn S. A., Inglod A. L., and Choley J. M. (1987) Correlation between the ATPase and microtubule translocating activities of sea urchin kinesin.Nature 328, 160–163.
Cohn S. A., Ingold A. L., and Scholey J. M. (1989) Quantitative analysis of sea urchin egg kinesin-driven microtubule motility.J. Biol. Chem. 264, 4290–4297.
Cyr J. L., Pfister K. K., Bloom G. S., Slaughter C. A., and Brady S. T. (1991) Molecular genetics of kinesin light chains: generation of multiple isoforms by alternative splicing.Proc. Natl. Acad. Sci. USA 88, 10,114–10,118.
Douglas M. G., McCammon M. T., and Vassarotti A. (1986) Targeting proteins into mitochondria.Microbiological Reviews 50, 166–178.
Elluru R. G., Pfister K. K., Bloom G. S., and Brady S. T. (1991) Phosphorylation of kinesin in the rat optic nerve/tract.J. Cell Biol. 115, 389a.
Erickson P. F. and Moore B. W. (1980) Investigation of the axonal transport of three acid soluble proteins (14-3-2, 14-3-3, and S-100) in the rabbit visual system.J. Neurochem. 35, 232–241.
Garner J. A. and Lasek R. J. (1981) Clathrin is axonally transported as part of slow component b: the microfilament complex.J. Cell Biol. 88, 172–178.
Garner J. A. and Lasek R. J. (1982) Cohesive axonal transport of the slow component b complex of polypeptides.J. Neurosci. 2, 1824–1835.
Gibbons L. R., Gibbons B. H., Mocz G., and Asai D. J. (1991) Multiple nucleotide binding sites in the sequence of dynein β heavy chain.Nature 352, 640–642.
Gilbert D. L., Adelman W. J., and Arnold J. M. eds. (1990)Squid as Experimental Animals. Plenum, New York.
Gilbert S. P. and Sloboda R. D. (1986) Identification of a MAP2-like ATP-binding protein associated with axoplasmic vesicles that translocates on isolated microtubules.J. Cell Biol. 103, 947–956.
Grafstein B. and Forman D. S. (1980) Intracellular transport in neurons.Physiol. Rev. 60, 1167–1283.
Hammerschlag R. and Brady S. T. (1989) Axonal transport and the neuronal cytoskeleton, inBasic Neurochemistry: Molecular, Cellular, and Medical Aspects, Siegel G. J., eds., Raven, New York, pp. 457–477.
Hammerschlag R. and Stone G. C. (1982) Membrane delivery by fast axonal transport.Trends Neurosci. 5, 12–15.
Hayden J. H. and Allen R. D. (1984) Detection of single microtubules in living cells: particle transport can occur in both directions along the same microtubule.J. Cell Biol. 99, 1785–1793.
Hiller W. K. (1989) A glossary of laboratory techniques used in kinesin research and a discussion of the role of technical understanding in creating illustrations. M. S. thesis. University of Texas Southwestern Medical Center, Dallas, TX.
Hirokawa N. (1982) The crosslinker system between neurofilaments, microtubules, and membranous organelles in frog axons revealed by quick-freeze, freeze fracture, deep-etching method.J. Cell Biol. 94, 129–142.
Hirokawa N., Pfister K. K., Yorifuji H., Wagner M. C., Brady S. T., and Bloom G. S. (1989) Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration.Cell 56, 867–878.
Hoffman P. N. and Lasek R. J. (1975) The slow component of axonal transport.J. Cell Biol. 66, 351–366.
Hollenbeck P. J. (1991) Kinesin heavy & light chains are phosphorylated in vivo in neurons.J. Cell Biol. 115, 390a.
Holzbaur E. L. F., Hammarback J. A., Paschal B. M., Kravit N. G., Pfister K. K., and Vallee R. B. (1991) Homology of a 150K Cytoplasmic Dynein-associated Polypeptide with theDrosophila GeneGlued.Nature 351, 579–583.
Howard J., Hudspeth A. J., and Vale R. D. (1989) Movement of microtubules by single kinesin molecules.Nature 342, 154–158.
Karlsson J.-O. and Sjostrand J. (1971) Transport of microtubule protein in axons of retinal ganglion cells.J. Neurochem. 18, 2209–2216.
Keith C. H. (1987) Slow transport of tubulin in the neurites of differentiated PC12 cells.Science 235, 337–339.
Kosik K. S., Orecchio L. D., Schnapp B., Inouye H., and Neve R. L. (1990) The primary structure and analysis of the squid kinesin heavy chain.J. Biol. Chem. 265, 3278–3283.
Kuczmarski E. R. and Rosenbaum J. L. (1979) Chick brain actin and myosin isolation and characterization.J. Cell Biol. 80, 341–355.
Kuznetsov S. A. and Gelfand V. I. (1986) Bovine brain kinesin is a microtubule-activated ATPase.Proc Natl. Acad. Sci. USA 83, 8530–8534.
Kuznetsov S. A., Vaisberg E. A., Rothwell S. W., Murphy D. B., and Gelfand V. I. (1989) Isolation of a 45-kDa fragment from the kinesin heavy chain with enhanced ATPase and microtubule-binding activities.J. Biol. Chem. 264, 589–595.
Kuznetsov S. A., Vaisberg E. A., Shanina N. A., Magretova N. N., Chernyak V. Y., and Gelfand V. I. (1988) The quaternary structure of bovine brain kinesin.EMBO J. 7, 353–356.
Lasek R. J. and Brady S. T. (1982) The structural hypothesis of axonal transport: two classes of moving elements, inAxoplasmic Transport, Weiss D. G., ed., Springer-Verlag, Berlin, pp. 397–405.
Lasek R. J. and Brady S. T. (1985) Attachment of transported vesicles to microtubules in axoplasm is facilitated by AMP-PNP.Nature 316, 645–647.
Leopold P. L., McDowall A. W., Pfister K. K., Bloom G. S., and Brady S. T. (1992) Association of kinesin with characterized membrane-bounded organelles.Cell Motility Cytoske. in press.
Levine J. and Willard M. (1981) Fodrin: axonally transported polypeptides associated with the internal periphery of many cells.J. Cell Biol. 90, 631–643.
McQuarrie I., Brady S., and Lasek R. (1980) Polypeptide composition and kinetics of SCa and SCb in sciatic nerve motor axons and optic axons of rat, in Soc.Neurosci. Abstr., p. 501.
Miller R. H. and Lasek R. J. (1985) Cross-bridges mediate anterograde and retrograde vesicle transport along microtubules in squid axoplasm.J. Cell Biol. 101, 2181–2193.
Morris J. and Lasek R. J. (1982) Stable polymers of the axonal cytoskeleton: the axoplasmic ghost.J. Cell Biol. 92, 192–198.
Murofushi H., Ikai A., Okuhara K., Kotani S., Aizawa H., Kumakura K., and Sakai H. (1988) Purification and characterization of kinesin from bovine adrenal medulla.J. Biol. Chem. 263, 12,744–12,750.
Murphy D. B., McNiven M. A., Wallis K. T., Kutznetsov S. A., and Gelfand V. I. (1989) The phosphorylation of kinesin does not affect its ATPase and translocating activities.J. Cell Biol. 109, 80a.
Nixon R. A. and Logvinenko K. B. (1986) Multiple fates of newly synthesized neurofilaments: Evidence for a stationary neurofilament network distributed nonuniformly along axons of retinal ganglion cells.J. Cell Biol. 102, 647–659.
Obar R. A., Collins C. A., Hammerback J. A., Shpetner H. S., and Vallee R. B. (1990) Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins.Nature 347, 256–261.
Oblinger M., Brady S., and McQuarrie I. (1982) Comparative compositional analysis of slowly transported axonal proteins in peripheral and central mammalian neurons.Soc. Neurosci. Abstr., p. 826.
Ogawa K. (1991) Four ATP-binding sites in the midregion of the β heavy chain of dynein.Nature 352, 643–645.
O'Shea E. K., Klemm J. D., Kim P. S., and Abler T. (1991) X-ray structure of the GNC4 leucine zipper, a two-stranded, parallel coiled coil.Science 254, 539–544.
Paschal B. M. and Vallee R. B. (1987) Retrograde transport by the microtubule-associated protein MAP 1C.Nature 330, 181–183.
Penningroth S. M., Rose P. M., and Peterson D. D. (1987) Evidence that the 116kDa component of kinesin binds and hydrolyzes ATP.FEBS Lett. 222, 204–210.
Pfister K. K., Wagner M. C., Stenoien D. L., Brady S. T., and Bloom G. S. (1989) Monoclonal antibodies to kinesin heavy and light chains stain vesicle-like structures, but not microtubules, in cultured cells.J. Cell Biol. 108, 1453–1463.
Porter M. E., Scholey J. M., Stemple D. L., Vigers G. P. A., Vale R. D., Sheetz M. P., and McIntosh J. R. (1987) Characterization of the microtubule movement produced by sea urchin egg kinesin.J. Biol. Chem. 262, 2794–2802.
Reinsch S. S., Mitchinson T. J., and Kirschner M. (1991) Microtubule polymer assembly and transport during axonal elongation.J. Cell Biol. 115, 365–379.
Sabry J. H., O'Connor T. P., Evans L., Toroian-Raymond A., Kirschner M., and Bentley D. (1991) Microtubule behavior during guidance of pioneer neuron growth cones in situ.J. Cell Biol. 115, 381–395.
Saxton W. M., Porter M. E., Cohn S. A., Scholey J. M., Raff E. C., and McIntosh J. R. (1988)Drosophila kinesin: characterization of microtubule motility and ATPase.Proc. Natl. Acad. Sci. USA 85, 1109–1113.
Schliwa M. (1984) Mechanisms of intracellular organelle transport.Cell Muscle Motil. 5, 1–81.
Schnapp B. J. and Reese T. M. (1989) Dynein is the motor for retrograde axonal transport of organelles.Proc Natl. Acad. Sci. USA 86, 1548–1552.
Schnapp B. J., Vale R. D., Sheetz M. P., and Reese T. S. (1985) Single microtubules from squid axoplasm support bidirectional movement of organelles.Cell 40, 455–462.
Scholey J. M., Heuser J., Yang J. T., and Goldstein L. S. B. (1989) Identification of globular mechanochemical heads of kinesin.Nature 338, 355–357.
Schroer T. A., Steuer E. R., and Sheetz M. P. (1989) Cytoplasmic dynein is a minus end-directed motor for membranous organelles.Cell 56, 937–946.
Shpetner H. S. and Vallee R. B. (1989) Identification of dynamin, a novel mechanochemical enzyme that mediates interactions between microtubules.Cell 59, 421–432.
Shpetner H. S., Paschal B. M., and Vallee R. B. (1988) Characterization of the microtubule-activated ATPase of brain cytoplasmic dynein (MAP 1C).J. Cell Biol. 107, 1001–1009.
Smith R. S. and Kendal W. S. (1984) The recovery of organelle transport and microtubule integrity in myelinated axons that are frozen and thawed.Can. J. Physiol. Pharmacol. 63, 292–297.
Tanaka E. and Kirschner M. (1991) Microtubule behavior in the growth cones of living neurons during axonal elongation.J. Cell Biol. 115, 345–363.
Tytell M., Black M. M., Garner J. A., and Lasek R. J. (1981) Axonal transport: each major rate component reflects the movement of distinct macromolecular complexes.Science 214, 179–181.
Tytell M., Brady S. T., and Lasek R. (1984) Axonal transport of a subclass of τ proteins: evidence for the regional differentiation of microtubules in neurons.Proc Natl. Acad. Sci. USA 77, 3042–3046.
Vale R. D., Reese T. S., and Sheetz M. P. (1985a) Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility.Cell 42, 39–50.
Vale R. D., Schnapp B. J., Mitchison T., Steuer E., Reese T. S., and Sheetz M. P. (1985b) Different axoplasmic proteins generate movement in opposite direction along microtubules in vivo.Cell 43, 623–632.
Vallee R. B. and Bloom G. S. (1991) Mechanisms of fast and slow axonal transport.Ann. Rev. Neurosci. 14, 59–92.
Vallee R. B., Sheptner H. S., and Paschal B. M. (1989) The role of dynein in retrograde transport.Trends Neurosci. 12, 66–70.
van der Bliek A. M. and Meyerowitz E. M. (1991) Dynamin-like protein encoded by the Drosophilashibire gene associated with vesicular traffic.Nature 351, 411–414.
Wagner M. C., Pfister K. K., Bloom G. S., and Brady S. T. (1989) Copurification of kinesin polypeptides with microtubule-stimulated Mg-ATPase activity and kinetic analysis of enzymatic properties.Cell Motil. Cytoskel. 12, 195–215.
Weisenberg R. C., Flynn J., Gao B. C., and Awodi S. (1988) Microtubule gelation-contraction in vitro and its relationship to component a of slow axonal transport.Cell Motil. Cytoskel. 10, 331–340.
Willard M. (1977) The identification of two intraaxonally transported polypeptides resembling myosin in some respects in the rabbit visual system.J. Cell Biol. 75, 1–11.
Willard M., Cowan W. M., and Vagelos P. R. (1974) The polypeptide composition of intraaxonally transported proteins: evidence for four transport velocities.Proc Natl. Acad. Sci. USA 71, 2183–2187.
Willard M., Wiseman M., Levine J., and Skene P. (1979) Axonal transport of actin in rabbit retinal ganglion cells.J. Cell Biol. 81, 581–591.
Wright B. D., Henson J. H., Wedaman K. P., Willy P. J., Morand J. N., and Scholey J. M. (1991) Subcellular localization and sequence of sea urchin kinesin heavy chain: evidence for its association with membranes in the mitotic apparatus and interphase cytoplasm.J. Cell Biol. 113, 817–833.
Yang J. T., Laymon R. A., and Goldstein L. S. B. (1989) A three-domain structure of kinesin heavy chain revealed by DNA sequence and microtubule binding analyses.Cell 56, 879–889.
Yang J. T., Saxton W. M., and Goldstein L. S. B. (1988) Isolation and characterization of the gene encoding the heavy chain ofDrosophila kinesin.Proc. Natl. Acad. Sci. USA 85, 1864–1868.
Yang J. T., Saxton W. M., Stewart R. J., Raff E. C., and Goldstein L. S. B. (1990) Evidence that the head of kinesin is sufficient for force generation and motility in vitro.Science 249, 42–47.
Yeh E., Driscoll R., Coletrera M., Olins A., and Bloom K. (1991) A dynamin-like protein encoded by yeast sporulation gene SPO15.Nature 349, 713–715.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cyr, J.L., Brady, S.T. Molecular motors in axonal transport. Mol Neurobiol 6, 137–155 (1992). https://doi.org/10.1007/BF02780549
Issue Date:
DOI: https://doi.org/10.1007/BF02780549