Department of Cell Biology

Duke University Medical Center




Sharyn Endow

Professor of Cell Biology


Campus Address

Mail: Box 3709
Room: 438 Jones Building
Phone: (919) 684-4311
email: endow001@mc.duke.edu



Research Activities

Our research focuses on the dynamics of chromosomes and the spindle, and the mechanisms that ensure proper chromosome transmission and inheritance. Several years ago we identified a kinesin-related microtubule motor protein, Ncd, that is required for normal chromosome distribution in Drosophila. Our current efforts are to determine the role of Ncd in chromosome segregation and define the molecular basis of the unexpected reversed polarity of Ncd translocation relative to kinesin.

We have localized the Ncd motor to mitotic spindles and spindle poles, including centrosomes, and shown that ncd mutants exhibit precocious splitting of centrosomes and frequent centrosome loss from poles. These findings indicate that Ncd prevents centrosomal splitting until late mitosis and attaches centrosomes to poles in wildtype spindles. We also showed that Kar3, a mitotic kinesin protein from S. cerevisiae, is a minus-end microtubule motor, like Ncd. Kar3 is a "slow" motor with the unusual ability to destabilize microtubules at their minus ends. Depolymerization of microtubules at spindle poles by Kar3 could contribute to slow poleward microtubule flux, facilitating poleward chromosome movement. Our work provides the first evidence for regulation of microtubule dynamics by a motor protein. Using phylogenetic analysis of available kinesin protein sequences, we found a unique subfamily of kinesin proteins predicted to consist only of minus-end kinesin motors like Ncd and Kar3, and to exist in most or all eukaryotes. The minus-end kinesin motors probably perform roles in mitosis that include attaching components of the mitotic apparatus to one another and mediating poleward chromosome movement by sliding microtubules and kinetochores poleward.

We are also carrying out biochemical, biophysical and structural studies to determine the mechanism by which Ncd and other kinesin motors function. These studies should help us understand the molecular basis of motor directionality, as well as the motor mechanism. The findings will be important in understanding the way the motors work in the cell.

Our work is leading to an understanding of the forces that drive meiotic and mitotic chromosome movement and the roles of force-producing motor proteins like Ncd. Normal segregation of chromosomes is necessary for formation of normal gametes in meiosis and somatic cells in mitosis. Disruption of chromosome segregation results in lethality and abnormal offspring in meiosis, and somatic abnormalities and cellular transformation in mitotically dividing cells.






Mitotic spindles in a live embryo of Drosophila decorated with the Ncd microtubule motor protein fused to the jellyfish green fluorescent protein (GFP).





Postdoctoral Position Opening!


Useful Links

Kinesin Home Page

Movie Page!!!

Selected Bibliography

  1. Endow, S.A., Henikoff, S., and Soler-Niedziela, L. 1990. Mediation of meiotic and early mitotic chromosome segregation in Drosophila by a protein related to kinesin. Nature 345: 81-83.
  2. Walker, R.A., Salmon, E.D., and Endow, S.A. 1990. The Drosophila claret segregation protein is a minus-end directed motor molecule. Nature 347: 780-782
  3. Endow, S.A., Kang, S.J., Satterwhite, L.L., Rose, M.D., Skeen, V.P. and Salmon, E.D. 1994. Yeast Kar3 is a minus-end microtubule motor protein that destabilizes microtubules preferentially at the minus ends. EMBO J. 13: 2708-2713.
  4. Endow, S.A. and Komma, D.J. 1996. Centrosome and spindle function of the Drosophila Ncd microtubule motor visualized in live embryos using Ncd-GFP fusion proteins. J. Cell Science 109: 2429-2442.
  5. Endow, S.A. and Komma, D.J. 1997. Spindle dynamics during meiosis in Drosophila oocytes. J. Cell Biol. 137: 1321-1336.
  6. Gulick, A.H., Song, H., Endow, S.A. and Rayment, I.R. 1998. X-ray crystal structure of the yeast Kar3 motor domain complexed with MgxADP to 2.3 A resolution. Biochemistry 37: 1769-1776.
  7. Endow, S.A. and Waligora, K.W. 1998. Determinants of kinesin motor polarity. Science 281: 1200-1202.
  8. Endow, S.A. and Komma, D.J. 1998. Assembly and dynamics of the astral:anastral meiosis II spindle of Drosophila oocytes. J. Cell Sci. 111: 2487-2495.
  9. Song, H. and Endow, S.A. 1998. Decoupling of nucleotide- and microtubule-binding sites in a kinesin mutant. Nature 396: 587-590.
  10. Endow, S.A. 1999. Determinants of molecular motor directionality. Nature Cell Biology 1:163-167.
  11. Endow, S.A. and Higuchi, H. 2000. A mutant of the motor protein kinesin that moves in both directions on microtubules. Nature 406: 913-916.
  12. Yun, M., Zhang, X., Park, C-G, Park, H-W. and Endow, S.A. 2001. A structural pathway for activation of the kinesin motor ATPase. EMBO J. 20: 2611-2618.

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