Faculty

Research Interests

We are interested in understanding the process of cell morphogenesis at the molecular level. Fission yeast Schizosaccharomyces pombe is an attractive model system for the study of cell form and -polarity because cells are cylindrical in shape and grow in a polarized manner. Moreover, polarized cell growth is regulated during the cell cycle and morphological changes are coupled with cell cycle progression. We have previously identif ied 19 genes which are necessary for various aspects of cell morphogenesis: genes required for the maintenance of cell polarity throughout the cell cycle, genes essential for the transition from monopolar to bipolar growth, genes which may act as positional markers for cell polarity and genes involved in the control of the actin and the microtubule cytoskeleton.

The three phenotypic categories of shape mutants. (a) Wildtype strain ade6-M210 leu1-32h-, (b) orb6-25, and (c) ban2-92. (Bar=5mm)

Our main area of investigation concerns the molecular mechanisms which coordinate cell morphogenesis with the cell cycle. We have found that the orb6 gene, which is required during interphase to maintain cell polarity, encodes a serine/threonine protein kinase, closely related to both the human myotonic dystrophy DM kinase and rho-associated kinase. A decrease in Orb6 protein levels leads to mitotic advance, while an increase in Orb6 protein levels delays mitosis by affecting the p34Cdc2 mitotic kinase. Thus the Orb6 protein kinase coordinates maintenance of cell polarity during interphase with the onset of mitosis. The similarity of Orb6 with Drosophila warts, which is thought to function as a tumor suppressor, and other genes in mammalian cells which affect cell shape suggests that its function in coordinating cell morphogenesis. with the cell cycle may be conserved in higher eukaryotes. The study of Orb6 in fission yeast will provide the opportunity to genetically dissect the mechanism of regulation of this family of kinases and to identify additional functions in the control of cell proliferation and cell morphogenesis. Our aim is to analyze the Orb6 pathway biochemically and to identify potential substrates and novel genes interacting with Orb6

A second area of investigation in the laboratory involves the analysis of novel components which control the microtubule cytoskeleton. Work with various microtubule mutants has shown that the microtubule cytoskeleton has a fundamental role in the control of cell polarity in fission yeast. This indicates that fission yeast can be useful as a model system for the study of microtubule based cell polarity, a process which is essential in mammalian cell morphogenesis.

Honors and Professional Activities

Member, American Society for Cell Biology (ASCB).
Member, American Society for Biochemistry and Molecular Biology (ASBMB)

Supported By:

Human Frontier Science Program
American Cancer Society
National Science Foundation
Sylvester Cancer Center

Selected Recent Publications

Gouget K., Verde F. and Barrientos A.. (2007) In Vivo Labeling and Analysis of Mitochondrial Translation Products in the budding and in the fission yeasts. Methods Mol Biol., in press.

Das M., Wiley D.J., Medina S., Vincent H., Larrea M., Oriolo A. and Verde F. (2007) Regulation of cell diameter, For3p localization and cell symmetry by fission yeast Rho-GAP Rga4p. MBC, 18:2090-2101 Check InCytes highlighting of our paper!

Kanai M., Kume K., Miyahara K., Sakai K., Nakamura K., Leonhard K., Wiley D., Verde F., Toda T. and Hirata D. (2005) Fission yeast MO25 protein is localized at SPB and septum and is essential for cell morphogenesis. EMBO J 24(17):3012-25.

Feierbach B., Verde F., and Chang F. (2004) Regulation of a formin complex by the microtubule plus end protein tea1p. J.Cell Biol., 165(5):697-707.

Oltra, E., Werner R., Verde F. and D’Urso G. (2004) A novel RING-finger-like protein Ini1 is required for cell cycle progression in fission yeast. J.Cell Sci 117(Pt 6):967-74.

Kim H., Yang P., Catanuto, P., Verde F., Lai H., Du H., Chang F., and Marcus, S. (2003) The kelch-repeat protein, Tea1, is a potential substrate target of the p21-activated kinase Shk1, in the fission yeast Schizosaccharomyces pombe. J. Biol. Chem. 278:30074-82.

Chang, F. and Verde, F. Control of cell polarity and cell morphogenesis. (2003) In: “Molecular Biology of Schizosaccharomyces pombe” Springer-Verlag, 255-267.

Wiley DJ, Marcus S., D’Urso G. and Verde, F. (2003) Control of cell polarity in fission yeast by association of Orb6p kinase with the highly conserved protein methyltransferase Skb1p. J. Biol. Chem. 278(27):25256-63.

Hou M., Wiley D., Verde F. and McCollum D. (2003) Mob2p interacts with Orb6p kinase to promote coordination of cell polarity with cell cycle progression. J. Cell Science, 116 (Pt. 1): 125-35.

Verde, F. (2001) Cell polarity: a tale of two Ts. Current Biology, Vol. 11, 600-602.

Bao S., Qyang Y., Yang P., Kim H., Du H., Bartholomeusz G., Pimental R., Verde F., Marcus S. (2001) The highly conserved protein methyltransferase, Skb1, is a mediator of hyperosmotic stress response in fission yeast, Schizosaccharomyces pombe. J. Biol. Chem. 276 (18): 14549-52.

Verde, F. (1998) On growth and form: control of cell morphogenesis in fission yeast. Curr. Op. Microbiol., 1 (6):712-718.

Verde, F., D.J. Wiley and P. Nurse, (1998) Fission yeast orb6, a ser/thr protein kinase related to mammalian rho-kinase and myotonic dystrophy kinase, interacts with pak1/shk1 and co-ordinates cell morphogenesis with the cell cycle. Proc. Natl. Acad. Sci. USA, 95, 7526-7531.

Tournebize, R., SSL Andersen , F. Verde, M. Dorée, E. Karsenti and A.A. Hyman, (1997) Distinct roles of PP1 and PP2A-like phosphatases in control of microtubule dynamics during mitosis. EMBO J 16(18), 5537-5549.

Yaffe, M.P., D. Hirata, F. Verde, M. Eddison and P. Nurse, (1996) Microtubule mediate mitochondrial distribution in fission yeast. Proc. Natl. Acad. Sci. USA, 93, 11664-11668

Verde, F., J. Mata and P. Nurse, (1995) Fission yeast cell morphogenesis: Identification of new genes and analysis of their role during the cell cycle. J. Cell Biol. 131(6), 1529-1538.