Skip to main content
SpringerLink
Log in

The nuclear/mitotic apparatus protein NuMA is a component of the somatodendritic microtubule arrays of the neuron

  • Published:
Journal of Neurocytology

Abstract

Neurons are terminally post-mitotic cells that utilize their microrubule arrays for the growth and maintenance of axons and dendrites rather than for the formation of mitotic spindles. Recent studies from our laboratory suggest that the mechanisms that organize the axonal and dendritic microtubule arrays may be variations on the same mechanisms that organize the mitotic spindle in dividing cells. In particular, we have identified molecular motor proteins that serve analogous functions in the establishment of these seemingly very different microtubule arrays. In the present study, we have sought to determine whether a non-motor protein termed NuMA is also a component of both systems. NuMA is a ~230 kDa structural protein that is present exclusively in the nucleus during interphase. During mitosis, NuMA forms aggregates that interact with microtubules and certain motor proteins. As a result of these interactions, NuMA is thought to draw together the minus-ends of microtubules, thereby helping to organize them into a bipolar spindle. In contrast to mitotic cells, post-mitotic neurons display NuMA both in the nucleus and in the cytoplasm. NuMA appears as multiple small particles within the somatodendritic compartment of the neuron, where its levels increase during early dendritic differentation. A partial but not complete colocalization with minus-ends of microtubules is suggested by the distribution of the particles during development and during drug treatments that alter the microtubule array. These observations provide an initial set of clues regarding a potentially important function of NuMA in the organization of microtubules within the somatodendritic compartment of the neuron.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahmad, F.J., Echeverri, C.J., Vallee, R.B. & Baas, P.W. (1998) Cytoplasmic dynein and dynactin are required for the transport of microtubules into the axon. Journal of Cell Biology 140, 246-56.

    Google Scholar 

  • Baas, P.W., Deitch, J.S., Black, M.M. & Banker, G.A. (1988) Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proceedings of the National Academy of Sciences USA 85, 8335-9.

    Google Scholar 

  • Baas, P.W., Slaughter, T., Brown, A. & Black, M.M. (1991) Microtubule dynamics in axons and dendrites. Journal of Neuroscience Research 30, 134-53.

    Google Scholar 

  • Baas, P.W. & Ahmad, F.J. (1993) The transport properties of axonal microtubules establish their polarity orientation.Journal of Cell Biology 120, 1427-37.

    Google Scholar 

  • Black, M.M. & Baas, P.W. (1989) The basis of polarity in the neuron. Trends in Neuroscience 12, 211-14.

    Google Scholar 

  • Blangy, A., Lane, H.A., D'Herin, P., Harper, M., Kress, M. & Nigg, E.A. (1995) Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83, 1159-69.

    Google Scholar 

  • Burton, P.R. (1988) Dendrites of mitral cell neurons contain microtubules of opposite polarity. Brain Research 437, 107-15.

    Google Scholar 

  • Compton, D.A., Yen, T.J. & Cleveland, D.W. (1991) Identification of novel centromere/kinetochoreassociated proteins using monoclonal antibodies generated against human mitotic chromosome scaffolds. Journal of Cell Biology 112, 1083-97.

    Google Scholar 

  • Compton, D.A., Szilak, I. & Cleveland, D.W. (1992) Primary structure of NuMA, an intranuclear protein that defines a novel pathway for segregation of proteins at mitosis. Journal of Cell Biology 116, 1395-1408.

    Google Scholar 

  • Compton, D.A. & Cleveland, D.W. (1994) NuMA, a nuclear protein involved in mitosis and nuclear reformation.Current Opinion in Cell Biology 6, 343-46.

    Google Scholar 

  • Compton, D.A. & Luo, C. (1995) Mutations of the predicted p34cdc2 phosphorylation sites in NuMAimpair the assembly of the mitotic spindle and block mitosis.Journal of Cell Science 108, 621-33.

    Google Scholar 

  • Dotti, C.G., Sullivan, C.A. & Banker, G.A. (1988) The establishment of polarity by hippocampal neurons in culture. Journal of Neuroscience 8, 121-30.

    Google Scholar 

  • Ferhat, L., Cook, C., Chauviere, M., Harper, M., Kress, M., Lyons, G.E. & Baas, P.W. (1998a) Expression of the mitotic motor protein Eg5 in postmitotic neurons: implications for neuronal development.Journal of Neuroscience 18, 7822-35.

    Google Scholar 

  • Ferhat, L., Kuriyama, R., Lyons, G.E. & Baas, P.W. (1998b) Expression of the motor protein CHO1/MKLP1 in postmitotic neurons. European Journal of Neuroscience 10, 1383-93.

    Google Scholar 

  • Gaglio, T., Saredi, A. & Compton, D.A. (1995) NuMA is required for the organization of microtubules into aster-like mitotic arrays. Journal of Cell Biology 131, 693-708.

    Google Scholar 

  • Gaglio, T., Saredi, A., Bingham, J.B., Hasbani, M.J., Gill, S.R., Schroer, T.A. & Compton, D.A. (1996) Opposing motor activities are required for the organization of the mammalian mitotic spindle pole. Journal of Cell Biology 135, 399-414.

    Google Scholar 

  • Goslin, K. & Banker, G. 1991. Rat hippocampal neurons in low-density culture. In Culturing Nerve Cells (edited by Banker, G. & Goslin, K.), pp 251-81.Cambridge: MIT Press.

    Google Scholar 

  • Heald, R., Tournebize, R., Blank, T., Scandaltzopoulos, R., Becker, P., Hyman, A.A. & Karsenti, E. (1996) Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature (London) 382, 420-5.

    Google Scholar 

  • Heidemann, S.R., Landers, J.M. & Hamborg, M.A. (1981) Polarity orientation of axonal microtubules.Journal of Cell Biology 91, 661-5.

    Google Scholar 

  • Higgins, D., Lein, P.J., Osterhout, D.J. & Johnson, M.I. (1991) Tissue culture of mammalian autonomic neurons. In Culturing Nerve Cells (edited by Banker, G. & Goslin K.), pp 177-205. Cambridge: MIT Press.

    Google Scholar 

  • Kallajoki, M., Weber, K. & Osborn, M. (1992) Ability to organize microtubules in taxol-treated mitotic PtK2 cells goes with the SPN antigen and not with the centrosome. Journal of Cell Science 102, 91-102.

    Google Scholar 

  • Luderus, M.E., den Blaauwen, J.L., de Smit, O.J., Compton, D.A. & van Driel, R. (1994) Binding of matrix attachment regions to lamin polymers involves single-stranded regions and the minor groove.Molecular Cell Biology 14, 6297-305.

    Google Scholar 

  • Maekawa, T., Leslie, R. & Kuriyama, R. (1991) Identification of a minus end-specific microtubule-associated protein located at the mitotic poles in cultured mammalian cells. European Journal of Cell Biology 54, 255-261.

    Google Scholar 

  • Maekawa, T. & Kuriyama, R. (1993) Primary structure and microtubule-interacting domain of the SP-H antigen: a mitotic map located at the spindle pole and characterized as a homologous protein to NuMA. Journal of Cell Science 105, 589-600.

    Google Scholar 

  • Merdes, A., Ramyar, K., Vechio, J.D. & Cleveland, D.W. (1996) Acomplex of NuMAand cytoplasmic dynein is essential for mitotic spindle assembly. Cell 87, 447-58.

    Google Scholar 

  • Merdes, A. & Cleveland, D.W. (1997) Pathways of spindle pole formation: different mechanisms; conserved components. Journal of Cell Biology 138, 953-56.

    Google Scholar 

  • Merdes, A. & Cleveland, D.W. (1998) The role of NuMA in the interphase nucleus. Journal of Cell Biology 111, 71-9.

    Google Scholar 

  • Price, C.M. & Pettijohn, D.E. (1986) Redistribution of the nuclear mitotic apparatus protein (NuMA) during mitosis and nuclear assembly. Experimental Cell Research 166, 295-311.

    Google Scholar 

  • Saredi, A., Howard, L. & Compton, D.A. (1997).Phosphorylation regulates the assembly of NuMA in a mammalian mitotic extract. Journal of Cell Biology 110, 1287-97.

    Google Scholar 

  • Sellitto, C. & Kuriyama, R. (1988) Distribution of a matrix component of the midbody during the cell cycle in chinese hamster ovary cells. Journal of Cell Biology 106, 531-9.

    Google Scholar 

  • Sharp, D.J., Yu, W. & Baas, P.W. (1995) Transport of dendritic microtubules establishes their nonuniform polarity orientation. Journal of Cell Biology 130, 93-104.

    Google Scholar 

  • Sharp D.J., Kuriyama, R. & Baas, P.W. (1996) Expression of a kinesin-related motor protein induces Sf9 cells to form dendrite-like processes with nonuniform microtubule polarity orientation. Journal of Neuroscience 16, 4370-75.

    Google Scholar 

  • Sharp, D.J., Yu, W., Ferhat, L., Kuriyama, R., Rueger, D.C. & Baas, P.W. (1997) Identification of a motor protein essential for dendritic differentiation.Journal of Cell Biology 138, 833-43.

    Google Scholar 

  • Tang, T.K., Tang, C.C., Chen, Y.-L. & Wu, C-W. (1993) Nuclear proteins of the bovine esophageal epithelium II. The NuMA gene gives rise to multiple mRNAs and gene products reactive with monoclonal antibody W1. Journal of Cell Biology 104, 244-60.

    Google Scholar 

  • Tang, T.K., Chieh-Ju, C., Chao, Y. & Wu, C-W. (1994) Nuclear mitotic apparatus protein (NuMA): spindle association, nuclear targeting and differential subcellular localization of various NuMA isoforms. Journal of Cell Science 107, 1389-1402.

    Google Scholar 

  • Tousson, A., Zeng, C., Brinkley, B.R. & Valdiria, M.M. (1991) Centrophilin: a novel mitotic spindle protein involved in microtubule nucleation. Journal of Cell Biology 112, 427-40.

    Google Scholar 

  • Verde, F., Berrez, J.-M., Antony, C. & Karsenti, E. (1991) Taxol-induced microtubule asters in mitotic extracts of Xenopus eggs: requirement for phosphorylated factors and cytoplasmic dynein. Journal of Cell Biology 112, 1177-87.

    Google Scholar 

  • Yang, C.H., Lambie, E.J. & Snyder, M. (1992) NuMA: an unusually long coiled-coil related protein in the mammalian nucleus. Journal of Cell Biology 116, 1303-17.

    Google Scholar 

  • Yu, W. & Baas, P.W. (1994) Changes in microtubule number and length during axon differentiation. Journal of Neuroscience 14, 2818-29.

    Google Scholar 

  • Yu, W., Sharp, D.J., Kuriyama, R., Mallik, P. & Baas, P.W. (1997) Inhibition of a mitotic motor protein compromises the formation of dendrite-like processes from N2a cells. Journal of Cell Biology 136, 659-68.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, The University of Wisconsin Medical School, Madison, WI, 53706

    Lotfi Ferhat, Crist Cook & Peter W. Baas

  2. Department of Cell Biology and Neuroanatomy, The University of Minnesota Medical School, Minneapolis, MN, 55455

    Ryoko Kuriyama

Authors
  1. Lotfi Ferhat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Crist Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryoko Kuriyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter W. Baas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter W. Baas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferhat, L., Cook, C., Kuriyama, R. et al. The nuclear/mitotic apparatus protein NuMA is a component of the somatodendritic microtubule arrays of the neuron. J Neurocytol 27, 887–899 (1998). https://doi.org/10.1023/A:1006949006728

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006949006728

Search

Navigation