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| FACULTY BIOGRAPHY |
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| Chloë Bulinski |
| Professor
Co-Director of Graduate Studies |
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| The polymerization and depolymerization dynamics of microtubules (MTs) are subject to exquisitely precise regulation in vivo, probably owing to the fact that small perturbations in MT dynamics are sufficient to arrest cell division, differentiation and motility processes. In fact, numerous chemotherapeutic drugs target MT dynamics in order to halt tumor cell proliferation, metastasis or viability; the slight alteration of MT dynamics produced by these drugs is often sufficient to launch cells on an apoptotic cascade. Our laboratory studies the regulation of MT dynamics and function during the cell cycle and differentiation, as well as in response to MT-antagonistic drugs.
MT-associated proteins (MAPs) are capable of modulating MTs, including their dynamics and their role in mitosis and vesicle transport. One MAP, ensconsin, which is present in a variety of human cells, does not regulate microtubule /dynamics. Recent experiments revealed that increased expression of ensconsin is deleterious to carcinoma cells treated with MT-stabilizing chemotherapeutics, e.g., Taxol (1), while a variety of biochemical experiments suggested that ensconsin's binding to MTs might be altered by Taxol treatment. To investigate this hypothesis, we used fluorescent speckle microscopy (FSM) a method with which one can image single molecules in vivo; it optimizes visibility of fluorescent molecules in living cells and reveals assembly dynamics, movement, and turnover of protein assemblies to follow the dynamics of ensconsin molecules' association/dissociation with MTs in vivo. We found that ensconsin normally existed in dynamic association with MTs, but in cells that were Taxol-treated, or had their MT dynamics halted by other means (i.e., depleting cellular ATP levels or extracting cells with detergent) ensconsin became more statically associated with the MT (2).
Quantifying ensconsin's residence time along the length of a MT by another technique, fluorescence recovery after photobleaching (FRAP) we found that the t1/2 of ensconsin's MT binding is rapidly increased up to 50-fold by decreasing the dynamics of the MTs to which the ensconsin is bound (2). These results suggest that ensconsin may function as a 'sensor' of MT dynamics, signaling to the cell that deleterious MT stabilization has occurred. We are currently testing this hypothesis.
 Another means by which cells can monitor MT dynamics is by monitoring the post-translational modification state of the tubulin within their MTs. For example, the protomers within stable MTs become modified by detyrosination. During myogenesis, MTs become extensively detyrosinated, and we have recently shown that, even when the MT stabilization takes place normally, this MT detyrosination is necessary for myogenic morphogenesis and expression of muscle-specific genes (3).
Other experiments show that the post-translational modification state of the MTs affects cell motility, as well. We are currently investigating the role of modified and unmodified MTs in cell migration, using two experimental motility systems.
MedLine Listing of Dr. Bulinski's Publications |
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Representative Recent Publications
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- Gruber, D., Chang, W., Faire, K., and Bulinski, J.C. (2001) Abundant expression of the microtubule-associated protein, ensconsin (E-MAP-115), alters the cellular response to Taxol. Cell Motil. Cytoskel. 49: 115-129. Article
- Bulinski, J.C., Odde, D., Howell, B., Salmon, E. D., and Waterman-Storer, C. M. (2001) Rapid dynamics of the binding of ensconsin to microtubules in vivo. J. Cell Sci 114 (21). Article
- Chang, W., Webster, D.R., Salam, A.A., Gruber, D, Prasad A., Eiserich, J.P., and Bulinski, J.C. (2002) Alteration of the C-terminal Amino Acid of Tubulin Specifically Inhibits Myogenic Differentiation. J. Biological Chemistry 227 (34). Article
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