Abstract
The formation and maintenance of neuronal synapses is dependent on the active transport of material between the cell body and the axon terminal. Cytoplasmic dynein is one motor for microtubule-based axonal transport. Two pools of cytoplasmic dynein have been identified in the axon. They are distinguished by their intermediate and light intermediate chain subunits. Each pool is transported at different rates down the axon in association with different proteins or organelles. This review presents several models to discuss the potential functional roles of these different pools of cytoplasmic dynein during axonal transport.
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BAAS, P. W. (1997) Microtubules and axonal growth. Current Opinion in Cell Biology 9, 29-36.
BAAS, P. W. & YU, W. (1996) A composite model for establishing the microtubule arrays of the neuron. Molecular Neurobiology 2, 145-161.
BAUCH, A., CAMPBELL, K. S. & RETH, M. (1998) Interaction of the CD5 cytoplasmic domain with the Ca2+/calmodulin-dependent kinase IIdelta. European Journal of Immunology 28, 2167-2177.
BOWMAN, A. B., PATEL-KING, R. S., BENASHSKI, S. E., MCCAFFERY, J. M., GOLDSTEIN, L. S. & KING, S. M. (1999) Drosophila roadblock and Chlamydomonas LC7: a conserved family of dynein-associated proteins involved in axonal transport, flagellar motility, and mitosis. Journal of Cell Biology 146, 165-180.
BRADY, S. T. (2000) Neurofilaments run sprints not marathons. Nature Cell Biology 2, E43-E45
BRADY, S. T. & SPERRY, A. O. (1995) Biochemical and functional diversity of microtubule motors in the nervous system. Current Opinion in Neurobiology 5, 551-558.
CREPIEUX, P., KWON, H., LECLERC, N., SPENCER, W., RICHARD, S., LIN, R. & HISCOTT, J. (1997) I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain. Molecular Cell Biology 17, 7375-7385.
DICTENBERG, J. B., ZIMMERMAN, W., SPARKS, C. A., YOUNG, A., VIDAIR, C., ZHENG, Y., CARRINGTON, W., FAY, F. S., DOXSEY, S. J. (1998) Pericentrin and gamma-tubulin form a protein complex and are organized into a novel lattice at the centrosome. Journal of Cell Biology 141, 163-174.
DILLMAN, DABNEY, L. P., KARKI, S., PASCHAL, B. M., HOLZBAUR, E. L. & PFISTER, K. K. (1996a) Functional analysis of dynactin and cytoplasmic dynein in slow axonal transport. Journal of Neuroscience 16, 6742-6752.
DILLMAN, J. F., DABNEY, L. P. & PFISTER, K. K. (1996b) Cytoplasmic dynein is associated with slow axonal Cytoplasmic dynein subunit heterogeneity 827 transport. Proceedings of the National Academy of Science USA 93, 141-144.
DILLMAN, J. F. & PFISTER, K. K. (1994) Differential phosphorylation in vivo of cytoplasmic dynein associated with anterogradely moving organelles. Journal of Cell Biology 127, 1671-1681.
DOXSEY, S. J., STEIN, P., EVANS, L., CALARCO, P. D. & KIRSCHNER, M. (1994) Pericentrin, a highly conserved centrosome protein involved in microtubule organization. Cell 76, 639-650.
EPSTEIN, E., SELA-BROWN, A., RINGEL, I., KILAV, R., KING, S. M., BENASHSKI, S. E., YISRAELI, J. K., SILVER, J. & NAVEH-MANY, T. (2000) Dynein light chain binding to a 3'-untranslated sequence mediates parathyroid hormone mRNA association with microtubules. Journal of Clinical Investigation 105, 505-512.
GEE, M. A., HEUSER, J. E. & VALLEE, R. B. (1997) An extended microtubule-binding structure within the dynein motor domain. Nature 390, 636-639.
GEPNER, J., LI, M., LUDMANN, S., KORTAS, C., BOYLAN, K., IYADURAI, S. J., MCGRAIL, M. & HAYS, T. S. (1996) Cytoplasmic dynein function is essential in Drosophila melanogaster. Genetics 142, 865-878.
GILL, S. R., CLEVELAND, D. W. & SCHROER, T. A. (1994) Characterization of DLC-A and DLC-B, two families of cytoplasmic dynein light chain subunits. Molecular Biology of the Cell 5, 645-654.
GRAFSTEIN, B. & FORMAN, D. S. (1980) Intracellular transport in neurons. Physiological Reviews 60, 1167-1283.
GRIMES, M. L., BEATTIE, E. & MOBLEY, W. C. (1997) A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA. Proceedings of the National Academy of Science USA 94, 9909-9914.
HABURA, A., TIKHONENKO, I., CHISHOLM, R. L. & KOONCE, M. P. (1999) Interaction mapping of a dynein heavy chain. Identification of dimerization and intermediate-chain binding domains. Journal of Biological Chemistry 274, 15447-15453.
HARADA, A., TAKEI, Y., KANAI, Y., TANAKA, Y., NONAKA, S. & HIROKAWA, N. (1998) Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein. Journal of Cell Biology 141, 51-59.
HEALD, R., TOURNEBIZE, R., BLANK, T., SANDALTZOPOULOS, R., BECKER, P., HYMAN, A. & KARSENTI, E. (1996) Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382, 420-425.
HIROKAWA, N. (1997) The mechanisms of fast and slow transport in neurons: identification and characterization of the new kinesin superfamily motors. Current Opinion in Neurobiology 7, 605-614.
HIROKAWA, N., NODA, Y. & OKADA, Y. (1998) Kinesin and dynein superfamily proteins in organelle transport and cell division. Current Opinion in Cell Biology 10, 60-73.
HIROKAWA, N., SATO-YOSHITAKE, R., YOSHIDA, T. & KAWASHIMA, T. (1990) Brain dynein (MAP1C) localizes on both anterogradely and retrogradely transported membranous organelles in vivo. Journal of Cell Biology 111, 1027-1037.
HISCOTT, J., BEAUPARLANT, P., CREPIEUX, P., DELUCA, C., KWON, H., LIN, R. & PETROPOULOS, L. (1997) Cellular and viral protein interactions regulating I kappa B alpha activity during human retrovirus infection. Journal of Leukocyte Biology 62, 82-92.
HOLLERAN, E. A., KARKI, S. & HOLZBAUR, E. L. (1998) The role of the dynactin complex in intracellular motility. International Review of Cytology 182, 69-109.
HUGHES, S. M., VAUGHAN, K. T., HERSKOVITS, J. S. & VALLEE, R. B. (1995) Molecular analysis of a cytoplasmic dynein light intermediate chain reveals homology to a family of ATPases. Journal of Cell Science 108, 17-24.
JAFFREY, S. R. & SNYDER, S. H. (1996) PIN: an associated protein inhibitor of neuronal nitric oxide synthase. Science 274, 774-777.
KARKI, S. & HOLZBAUR, E. L. (1995) Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex. Journal of Biological Chemistry 270, 28806-28811.
KIM, A. J. & ENDOW, S. A. (2000) A kinesin family tree. Journal of Cell Science 113, 3681-3682.
KING, S. M. (2000a) AAA domains and organization of the dynein motor unit. Journal of Cell Science 113, 2521-2526.
KING, S. M. (2000b) The dynein microtubule motor. Biochimica et Biophysica Acta 1496, 60-75.
KING, S. M., BARBARESE, E., DILLMAN, J. F., BENASHSKI, S. E., DO, K. T., PATEL-KING, R. S. & PFISTER, K. K. (1998) Cytoplasmic dynein contains a family of differentially expressed light chains. Biochemistry 37, 15033-15041.
KING, S. M., BARBARESE, E., DILLMAN, J. F., III, PATEL-KING, R. S., CARSON, J. H. & PFISTER, K. K. (1996a) Brain cytoplasmic and flagellar outer arm dyneins share a highly conserved Mr 8,000 light chain. Journal of Biological Chemistry 271, 19358-19366.
KING, S. M., DILLMAN, J. F., BENASHSKI, S. E., LYE, R. J., PATEL-KING, R. S. & PFISTER, K. K. (1996b) The mouse t-complex-encoded protein Tctex-1 is a light chain of brain cytoplasmic dynein. Journal of Biological Chemistry 271, 32281-32287.
KING, S. M., WILKERSON, C. G. & WITMAN, G. B. (1991) The Mr 78,000 intermediate chain of Chlamydomonas outer arm dynein interacts with alpha-tubulin in situ. Journal of Biological Chemistry 266, 8401-8407.
KING, S. M. & WITMAN, G. B. (1990) Localization of an intermediate chain of outer arm dynein by immunoelectron microscopy. Journal of Biological Chemistry 265, 19807-19811.
LASEK, R. J. (1986) Polymer sliding in axons. Journal of Cell Science S5, 161-179.
LASEK, R. J. & BRADY, S. T. (1985) Attachment of transported vesicles to microtubules in axoplasm is facilitated by AMP-PNP. Nature 316, 645-647.
LI, J. Y., PFISTER, K. K., BRADY, S. T. & DAHLSTROM, A. (2000) Cytoplasmic dynein conversion at a crush injury in rat peripheral axons. Journal of Neuroscience Research 61, 151-161.
LUKASHOK, S. A., TARASSISHIN, L., LI, Y. & HORWITZ, M. S. (2000) An adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis complexes with dynein and a small GTPase. Journal of Virology 74, 4705-4709.
LYON, M. F. (1986) Male sterility of the mouse t-complex is due to homozygosity of the distorter genes. Cell 44, 357-363.
MARTIN, M., IYADURAI, S. J., GASSMAN, A., GINDHART, J. G. J., HAYS, T. S. & SAXTON, W. M. (1999) Cytoplasmic dynein, the dynactin complex, and kinesin are interdependent and essential for fast axonal transport. Molecular Biology of the Cell 10, 3717-3728.
MOU, T., KRAAS, J. R., FUNG, E. T. & SWOPE, S. L. (1998) Identification of a dynein molecular motor component in Torpedo electroplax; binding and phosphorylation of Tctex-1 by Fyn. FEBS Letters 435, 275-281.
NAGANO, F., ORITA, S., SASAKI, T., NAITO, A., SAKAGUCHI, G., MAEDA, M., WATANABE, T., KOMINAMI, E., UCHIYAMA, Y. & TAKAI, Y. (1998) Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein. Implication in dynein-dependent vesicle transport. Journal of Biological Chemistry 273, 30065-30068.
NAISBITT, S., VALTSCHANOFF, J., ALLISON, D. W., SALA, C., KIM, E., CRAIG, A. M., WEINBERG, R. J. & SHENG, M. (2000) Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein. Journal of Neuroscience 20, 4524-4534.
NIXON, R. A (1998) The slow axonal transport debate. Trends in Cell Biology 8, 100
NURMINSKY, D. I., NURMINSKAYA, M. V., BENEVOLENSKAYA, E. V., SHEVELYOV, Y. Y., HARTL, D. L. & GVOZDEV, V. A. (1998) Cytoplasmic dynein intermediate-chain isoforms with different targeting properties created by tissue-specific alternative splicing. Molecular Cell Biology 18, 6816-6825.
PASCHAL, B. M., KING, S. M., MOSS, A. G., COLLINS, C. A., VALLEE, R. B. & WITMAN, G. B. (1987) Isolated flagellar outer arm dynein translocates brain microtubules in vitro. Nature 330, 672-674.
PASCHAL, B. M., MIKAMI, A., PFISTER, K. K. & VALLEE, R. B. (1992) Homology of the 74-kD cytoplasmic dynein subunit with a flagellar dynein polypeptide suggests an intracellular targeting function. Journal of Cell Biology 118, 1133-1143.
PAZOUR, G. J., DICKERT, B. L. & WITMAN, G. B. (1999) The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. Journal of Cell Biology 144, 473-481.
PFISTER, K. K. (2000) Cytoplasmic dynein and microtubule transport in the axon: the action connection. Molecular Neurobiology 20, 81-91.
PFISTER, K. K., SALATA, M. W., DILLMAN, J. F., TORRE, E. & LYE, R. J. (1996a) Identification and developmental regulation of a neuron-specific subunit of cytoplasmic dynein. Molecular Biology of the Cell 7, 331-343.
PFISTER, K. K., SALATA, M. W., DILLMAN, J. F., VAUGHAN, K. T., VALLEE, R. B., TORRE, E. & LYE, R. J. (1996b) Differential expression and phosphorylation of the 74-kDa intermediate chains of cytoplasmic dynein in cultured neurons and glia. Journal of Biological Chemistry 271, 1687-1694.
PORTER, M. E., BOWER, R., KNOTT, J. A., BYRD, P. & DENTLER, W. (1999) Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas. Molecular Biology of the Cell 10, 693-712.
PRAHLAD, V., HELFAND, B. T., LANGFORD, G. M., VALE, R. D. & GOLDMAN, R. D. (2000) Fast transport of neurofilament protein along microtubules in squid axoplasm. Journal of Cell Science 113, 3939-3946.
PUROHIT, A., TYNAN, S. H., VALLEE, R. & DOXSEY, S. J. (1999) Direct interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization. Journal of Cell Biology 147, 481-492.
PUTHALAKATH, H., HUANG, D. C., O'REILLY, L. A., KING, S. M. & STRASSER, A. (1999) The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Molecular Cell 3, 287-296.
REYNOLDS, A. J., BARTLETT, S. E. & HENDRY, I. A. (1998) Signalling events regulating the retrograde axonal transport of 125I-beta nerve growth factor in vivo. Brain Research 798, 67-74.
RICCIO, A., PIERCHALA, B. A., CIARALLO, C. L. & GINTY, D. D. (1997) An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science 277, 1097-1100.
ROY, S., COFFEE, P., SMITH, G., LIEM, R. K., BRADY, S. T. & BLACK, M. M. (2000) Neurofilaments are transported rapidly but intermittently in axons: implications for slow axonal transport. Journal of Neuroscience 20, 6849-6861.
SCHAFER, D. A., GILL, S. R., COOPER, J. A., HEUSER, J. E. & SCHROER, T. A. (1994) Ultrastructural analysis of the dynactin complex: an actin-related protein is a component of a filament that resembles F-actin. Journal of Cell Biology 126, 403-412.
SCHNAPP, B. J. & REESE, T. S. (1989) Dynein is the motor for retrograde axonal transport of organelles. Proceedings of the National Academy of Science USA 86, 1548-1552.
SCHNORRER, F., BOHMANN, K. & NUSSLEIN-VOLHARD, C. (2000) The molecular motor dynein is involved in targeting swallow and bicoid RNA to the anterior pole of Drosophila oocytes. Nature Cell Biology 2, 185-190.
SHAH, J. V., FLANAGAN, L. A., JANMEY, P. A. & LETERRIER, J. F. (2000) Bidirectional translocation of neurofilaments along microtubules mediated in part by Dynein/Dynactin. Molecular Biology of the Cell 11, 3495-3508.
SIGNOR, D., WEDAMAN, K. P., OROZCO, J. T., DWYER, N. D., BARGMANN, C. I., ROSE, L. S. & SCHOLEY, J. M. (1999) Role of a class DHC1b dynein in retrograde transport of IFT motors and IFT raft particles along cilia, but not dendrites, in chemosensory neurons of living Caenorhabditis elegans. Journal of Cell Biology 147, 519-530.
STEFFEN, W., HODGKINSON, J. L. & WICHE, G. (1996) Immunogold localisation of the intermediate chain within the protein complex of cytoplasmic dynein. Journal of Structural Biology 117, 227-235.
STEFFEN, W., KARKI, S., VAUGHAN, K. T., VALLEE, R. B., HOLZBAUR, E. L., WEISS, D. G. & KUZNETSOV, S. A. (1997) The involvement of the intermediate chain of cytoplasmic dynein in binding the motor complex to membranous organelles of Xenopus oocytes. Molecular Biology of the Cell 8, 2077-2088.
SUSALKA, S. J., HANCOCK, W. O. & PFISTER, K. K. (2000) Distinct cytoplasmic dynein complexes are transported by different mechanisms in axons. Biochimica et Biophysica Acta 1496, 76-88.
TAI, A. W., CHUANG, J. Z., BODE, C., WOLFRUM, U. & SUNG, C. H. (1999) Rhodopsin's carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1. Cell 97, 877-887.
TYNAN, S. H., GEE, M. A. & VALLEE, R. B. (2000a) Distinct but overlapping sites within the cytoplasmic dynein heavy chain for dimerization and for intermediate chain and light intermediate chain binding. Journal of Biological Chemistry 275, 32769-32774.
TYNAN, S. H., PUROHIT, A., DOXSEY, S. J. & VALLEE, R. B. (2000b) Light intermediate chain 1 defines a functional subfraction of cytoplasmic dynein which binds to pericentrin. Journal of Biological Chemistry 275, 32763-32768.
VALLEE, R. B., SHPETNER, H. S. & PASCHAL, B. M. (1989) The role of dynein in retrograde axonal transport. Trends in Neuroscience 12, 66-70.
VAUGHAN, K. T. & VALLEE, R. B. (1995) Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued. Journal of Cell Biology 131, 1507-1516.
WANG, L., HO, C. L., SUN, D., LIEM, R. K. & BROWN, A. (2000) Rapid movement of axonal neurofilaments interrupted by prolonged pauses. Nature Cell Biology 2, 137-141.
WATERMAN-STORER, C. M., KARKI, S. & HOLZBAUR, E. L. (1995) The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1). Proceedings of the National Academy of Science USA 92, 1634-1638.
WATERMAN-STORER, C. M., KARKI, S. B., KUZNETSOV, S. A., TABB, J. S., WEISS, D. G., LANGFORD, G. M. & HOLZBAUR, E. L. (1997) The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. Proceedings of the National Academy of Science USA 94, 12180-12185.
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Susalka, S.J., Pfister, K.K. Cytoplasmic dynein subunit heterogeneity: implications for axonal transport. J Neurocytol 29, 819–829 (2000). https://doi.org/10.1023/A:1010995408343
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DOI: https://doi.org/10.1023/A:1010995408343