257 Weill Hall
Professor of Cell Biology
Member of the Weill Institute for Cell and Molecular Biology
Tony Bretscher is a Professor of Cell Biology in the Department of Molecular Biology and Genetics and is a member of the Weill Institute for Cell and Molecular Biology (Weill Institute). He is a member of the Graduate Fields of Biochemistry, Molecular and Cell Biology, and Genetics and Development. After training as a physicist at the University of Cambridge, he obtained his Ph.D. in genetics from the University of Leeds, studying gene regulation in E. coli. From there he went as an EMBO Fellow to the Department of Biochemistry, Stanford University, where he worked with Dale Kaiser on the genetics of cell-cell interactions during development in Myxococcus xanthus. He then went as a Max Planck Society Fellow to the Department of Biochemistry, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany, where he began his studies in cell biology with Klaus Weber. In 1980 he was appointed to the faculty in the Cell Biology Department at Southwestern Medical School in Dallas, Texas. He moved to Cornell in 1981. He has served on the Editorial Boards of the Journal of Biological Chemistry and Molecular Biology of the Cell, and is currently on the Editorial Boards of the Journal of Cell Biology and Journal of Cell Science.
He is also an author of the new edition of the Lodish et al. Molecular Cell Biology textbook.
We are interested in the functional organization and regulation of microfilaments in eucaryotic cells. Microfilaments, which are composed of actin filaments and associated proteins, are involved in a host of functions, including the determination of cellular shape and providing the machinery for a variety of motile processes. We are using diverse biochemical, structural, genetic and cell biological approaches to investigate the general principles underlying microfilament structure and function in eucaryotic cells. Two major projects are underway.
The first is a detailed investigation into the molecular organization of the microfilaments that make up the cytoskeleton of microvilli present on intestinal epithelial cells. In this work we are purifying and characterizing the various microfilament-associated proteins (including villin, fimbrin, brush border myosin I, and ezrin) and, together with ultrastructural studies, are piecing together the precise function of each component. We then explore whether related proteins perform similar functions in other, less easily studied, microfilament arrangements. Current studies suggest that ezrin performs a central role in coordinating cell structure with membrane traffick in the apical aspect of epithelial cells.
The second major project exploits the yeast Saccharomyces cerevisiae for a combined biochemical and genetic approach to the structure and function of a microfilament in this simple eucaryote. We are presently identifying, purifying and characterizing microfilament-associated proteins related to those under study in higher eucaryotic cells. Over the last few years, we have shown that one major component of the yeast actin cytoskeleton, namely the polarized actin cables that run from the bud into the mother cell, are polarized highways for the delivery of secretory vesicles for cell growth, as well as providing the underlying polarity for organelle segregation during the cell cycle. Working with the actin cables is a myosin-V molecular motor that carries cargoes along the cables to their destination. Our goal is to understand at the molecular level how cables are established, and how they are used by the myosin-V to deliver their cargo, both of which have to be regulated in a cell cycle-dependent manner.
Click here to view Dr. Bretscher's PubMed listings.
Publications since the year 2000 (out of a total of about 120):
Pearson, M., Reczek, D., Bretscher, A. & Karplus, P. A. (2000). Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin-binding tail domain. Cell 101, 259-270.
Pruyne, D. & Bretscher, A. (2000) . Polarization of Cell Growth in Yeast. I. Establishment and Maintenance of Polarity States. J. Cell Sci.113, 365-375
Pruyne, D. & Bretscher, A. (2000) . Polarization of Cell Growth in Yeast. II. The role of the cortical actin cytoskeleton. J. Cell Sci.113, 571-585.
Berryman, M. & Bretscher, A. (2000). Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that Associates with the actin cytoskeleton of Placental Microvilli. Mol. Biol. Cell. 11, 1509-1521.
Bretscher, A. (2000). Functional genomics at Cornell: The opportunities and challenges. Arts & Sciences Newsletter. Vol. 21 (2) p1-3.
Bretscher, A., Chambers, D., Nguyen, R. & Reczek, D. (2000) ERM-merlin and EBP50 protein families in plasma membrane organization and function. Ann. Rev. Cell & Devel. Biol. 16, 113-143.
Yin, H., Pruyne, D., Huffaker, T. & Bretscher, A. (2000). Myosin V orientates the mitotic spindle in yeast. Nature 406, 1013-1015.
Bretscher, A. (2000). The cytoskeleton: from regulation to function. EMBO Reports 1, 473-476.
Melendez-Vasquez, C. V., Rios, J. C., Xanazzi, G., Lambert, S., Bretscher, A. & Salzer, J. (2001). Nodes of Ranvier form in association with ERM-positive Schwann cell processes. Proc. Natl. Acad. Sci. USA 98, 1235-1240
Nuygen, R., Reczek, D. & Bretscher, A. (2001). Heirachy of N- and C-ERMAD associations and common ligands between ezrin and merlin. J. Biol Chem. 276, 7621-7629.
Reczek, D. & Bretscher, A. (2001) Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP. J. Cell Biol. 153, 191-206.
Ho, J. & Bretscher, A. (2001). Ras regulates the polarity of the yeast actin cytoskeleton through the stress response pathway. Mol. Biol. Cell 12, 1541-1555.
Kishi, M., Liu, X., Hirakawa, T., Reczek, D., Bretscher, A. & Ascoli, M. (2001). Identification of two distinct structural motifs that when added to the C-terminal tail of the rat LH receptor redirect the internalized hormone receptor complex from a degradation to a recycling pathway. Molecular Endocrinology 15, 1624-1635.
Berryman, M. & Bretscher, A. (2001) Immunoblot detection of antigens in immunoprecipitates. BioTechniques 31, 1-2.
Ingraffea, J., Reczek, D. & Bretscher, A. (2002). Distinct cell type expression of EBP50 and E3KARP: EBP50 is generally expressed with ezrin in specific epithelia, whereas E3KARP is not. Europ. J. Cell Biol. 81, 61-68.
Evangelista, M., Pruyne, D., Amberg, D., Boone, C. & Bretscher, A. (2002). Formins direct Arp2/3-independent actin filament assembly to polarize cell growth in yeast. Nature Cell Biology, 4, 32-41.
Schott, D., Collins, R. N. & Bretscher, A. (2002). Secretory vesicle transport velocity in living cells depends on the myosin-V lever-arm length. J. Cell Biol. 156, 35-39.
Hoe, N. P., Ireland, R. M., Gowen, B. B., Dorward, D. W., Liu, M., Burns, E. H., Culnan, D. M., Bretscher, A. & Musser, J. M. (2002) Insight into the molecular mechanism of pathogen durability and epidemics: Group A Streptococcus inhibitor of complement diminishes bacterial adherence to human epithelial cells. Proc. Natl. Acad. Sci. USA 99, 7646-7651.
Pruyne, D., Evangelista, M., Yang, C., Bi., E., Zigmond, S., Bretscher, A. & Boone, C. (2002) Role of formins in actin assembly: nucleation and barbed end association. Science 297, 612-615.
Bretscher, A., Edwards, K. & Fehon, R. (2002) ERM proteins and merlin: integrators at the cell cortex. Nature Reviews: Molecular and Cell Biology 3, 586-599.
Schott, D., Huffaker, T. & Bretscher, A. (2002). Microfilaments and microtubules: the news from yeast. Curr. Opin. Microbiol. 5, 564-574.
Smith, W.J., Nassar, N., Bretscher, A., Cerione, R. A. & Karplus, P.A. (2003). Structure of the active FERM Domain of Ezrin: conformational and mobility changes identify keystone interactions. J. Biol. Chem. 278, 4949-4956.
Bretscher A. (2003). Polarized growth and organelle segregation in yeast - the tracks, motors, and receptors. J. Cell Biol. 160, 811-816.
Dong, Y., Pruyne, D. & Bretscher, A. (2003). Two Rho pathways converge to regulate formin-dependent actin assembly in yeast. J. Cell Biol. 161, 1081-1092.
Gundersen, G.G. & Bretscher, A. (2003). Microtubule asymmetry.. Science 300, 2040-2041.
Finnerty, C., Chambers, D., Ingraffea, J., Faber, H. R., Karplus, P. A. & Bretscher, A. (2004) The EBP50-moesin interaction: structural analysis of a binding site regulated by direct masking on the FERM domain. J. Cell Sci. 117, 1547-1552..
Tong AH, Lesage G, Bader GD, Ding H, Xu H, Xin X, Young J, Berriz GF, Brost RL, Chang M, Chen Y, Cheng X, Chua G, Friesen H, Goldberg DS, Haynes J, Humphries C, He G, Hussein S, Ke L, Krogan N, Li Z, Levinson JN, Lu H, Menard P, Munyana C, Parsons AB, Ryan O, Tonikian R, Roberts T, Sdicu AM, Shapiro J, Sheikh B, Suter B, Wong SL, Zhang LV, Zhu H, Burd CG, Munro S, Sander C, Rine J, Greenblatt J, Peter M, Bretscher A, Bell G, Roth FP, Brown GW, Andrews B, Bussey H, Boone C. (2004) Global mapping of the yeast genetic interaction network. Science 303, 808-13
Nawrot, M., West, K., Huang, J., Possin, D. E., Bretscher, A., Crabb, J. W and Saari, J. C. (2004). Cellular retinaldehyde-binding protein interacts with ERM-binding phosphoprotein 50 in retinal pigment epithelium. Investigative Ophthalmology and Visual Science 45(2):393-401.
Pruyne, D., Legesse-Miller, A., Gao, L., Dong, Y. & Bretscher, A. (2004) Mechanisms of polarized growth and organelle segregation in yeast. Ann. Rev. Cell Dev. Biol. 20, 559-591.
Pruyne, D., Gao., L., Bi., E. & Bretscher A. (2004) Stable and dynamic axes of polarity utilize distinct forming isoforms in budding yeast.. Mol. Biol. Cell, 15, 4971-4989.
Hayashi, H., Szászi1, K., Coady-Osberg, N., Furuya, W., Bretscher, A. P., Orlowski, J., & Grinstein, S. (2004). Inhibition and Redistribution of NHE3, the Apical Na+/H+ Exchanger, by Clostridium difficile Toxin B. J. Gen. Physiol. 123, 491-504.
Chambers, D. & Bretscher, A. (2005). Ezrin mutants affecting dimerization and activation. Biochemistry, 44, 3926-3932.
Bretscher, A. (2005) Microtubule tips redirect actin assembly. Dev. Cell 8, 458-459.
Legesse-Miller, A., Zhang S, Santiago-Tirado, F. H. , Van Pelt, C. K, Bretscher, A. (2006). Regulated Phosphorylation of Budding Yeast's Essential Myosin-V Heavy Chain, Myo2p. Mol. Cell Biol. 17, 1812-1821.
Hanono, A., Garbett, D., Reczek, D., Chambers, D. N. & Bretscher, A. (2006). EPI64 regulates microvillar sub-domains and structure. J. Cell Biol. 175, 803-813.
Li, Q., Nance, M. R., Kulikauskas, R., Nyberg, K., Fehon, R., P., Karplus, P. A., Bretscher, A. & Tesmer, J. J. G. (2006). Self-masking in an intact ERM-merlin protein: an active role for the central a-helical domain. J. Mol. Biol. 365,1446-59
Bruce, B., Khanna, G. , Landberg, G., Jirström, K., Powell, C., Borczuk, A., Keller, E.T., Wojno, K.J., Meltzer, P., Baird, K., McClatchey, A., Bretscher, A., Hewitt, S. M. & Khanna, C. (2007). Expression of the Cytoskeleton Linker Protein Ezrin in Human Cancers. Clinical and Experimental Metastasis 24, 69-78.Amin, N.M., Hu, K., Pruyne, D., Terzic, D., Bretscher, A., Liu, J. (2007) A Zn-finger/FH2-domain containing protein, FOZI-1, acts redundantly with CeMyoD to specify striated body wall muscle fates in the Caenorhabditis elegans postembryonic mesoderm. Development. 134:19-29.