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Sharyn
Endow, Ph.D.
(Biology, Yale University)
Professor, Department of Cell Biology
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Research
in my laboratory focuses on spindle and chromosome dynamics,
and the mechanisms that ensure proper chromosome distribution
in dividing cells. Work over the past 10 years has identified
molecular motors as the force-generating proteins that
drive movements of the spindle and chromosomes in meiosis
and mitosis. We are currently trying to understand the
mechanism of motor function, including the molecular basis
of motor directionality, and the contributions of motor
proteins to spindle and chromosome dynamics during cell
division.
We are using molecular genetics to determine the basis
of the unusual motility of the Ncd microtubule motor protein,
discovered in my laboratory. The Ncd motor is required
for proper spindle assembly in oocytes and early embryos
of Drosophila. We showed previously that Ncd moves on
microtubules in the opposite direction as kinesin, the
founding member of the protein family to which Ncd belongs.
By constructing chimeric Ncd-kinesin motor proteins, we
identified residues required for the 'reversed' movement
of Ncd compared to kinesin. We recently mutated single
amino acid residues of Ncd and converted it into a motor
that lacks directionality and moves either towards the
microtubule plus or minus end. Analysis of the mutant
motor showed that the minus-end directionality of wild-type
Ncd is due to a large conformational change that occurs
when the motor binds to a microtubule. We are using mutants
to trap the motor in different conformations to visualize
this and other changes that occur in the motor as it moves
along a microtubule. The mutants are then transformed
into Drosophila as fusions to the green fluorescent protein
to obtain information about their effects on spindle and
chromosome dynamics in live cells.
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Email
endow001@mc.duke.edu
450 Sands Building, Box 3709
Duke University Medical Center
Durham, NC 27710
Telephone 919-684-4311 |
Selected
Publications
Hirose, K., Akimaru, E., Akiba,
T., Endow, S.A., and Amos, L.A. 2006. Large conformational changes
in a kinesin motor catalyzed by interaction wih microtubules.
Molecular Cell 23: 913-923. -PDF- SuppDataPDF
Sciambi, C.J., Komma, D.J., Sköld,
H.N., Hirose, K. and Endow, S.A. 2005. A bidirectional
kinesin motor in live Drosophila embryos. Traffic
6:1036-1046. -PDF-
Chu, H.M.A., Yun, M., Anderson,
D.E., Sage, H., Park, H., and Endow, S.A. 2005. Kar3
interaction with Cik1 alters motor structure and function.
EMBO J., advance online publication 18 August 2005; doi
10.1038/sj.emboj.7600790. -PDF-
Skold, H.N., Komma, D.J., and Endow,
S.A. 2005. Assembly pathway of the anastral Drosophila oocyte
meiosis I spindle. J. Cell Sci. 118, 1745-1755. -PDF-
Higuchi, H., Bronner, C.E., Park, H-W and Endow,
S.A. 2004. Rapid double 8-nm steps by a kinesin mutant.
EMBO J. 23, 2993-2999 advance online publication 15
July 2004; doi: 10.1038/sj.emboj.7600306. -PDF-
Dagenbach, E.M. and Endow, S.A. 2004.
A new kinesin tree. J. Cell Sci. 117, 3-7. -PDF-
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. -PDF-
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. -PDF-
Endow, SA: Determinants of molecular motor directionality.
Nature Cell Biology 1999; 1: 163-167. -PDF-
Endow SA, and Komma DJ: Assembly and dynamics of an anastral:astral
spindle: the meiosis II spindle of Drosophila oocytes.
J Cell Sci 1998; 111: 2487-95 -PDF-
Endow SA, and Waligora KW: Determinants of kinesin motor
polarity. Science 1998; 281: 1200-2 -PDF-
Song H and Endow SA: 1998. Decoupling
of nucleotide- and microtubule-binding
sites in a kinesin mutant. Nature 396: 587-590. -PDF-
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