Research Interests
I have worked for many years on the mechanisms and control of the cell cycle and of cell differentiation in yeasts (both the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe). These (relatively) simple, experimentally tractable model organisms have provided much of our current knowledge of the eukaryotic cell cycle and thus have served as a major source of the ideas that have guided research on the mammalian cell cycle and its aberrant behavior in cancer cells.

More recently, my lab has been studying some aspects of the cell cycle and cell differentiation in Drosophila, another centrally important model organism. Thus, although we do not study cancer directly, it is fair to say that our work has provided, and will undoubtedly continue to provide, many ideas and reagents that are important to those working more directly on the mechanisms of cancer causation.

Most of our current research deals with the control of cellular morphogenesis and of the cell division cycle and with the relationship between the two. We use a mixture of classical genetic, molecular genetic, microscopic and biochemical methods. We are studying the structure and function of the cytoskeletal elements that are responsible for morphogenetic activities, the signaling systems that provide positional information to the cytoskeleton, and the means by which the morphogenetic activities are coordinated with other cell-cycle events. We are currently concentrating on three main problems.

First, we are exploring the roles of positional markers in the cell cortex and of a GTPase cascade in controlling the selection of axes of polarization and the subsequent establishment of cytoskeletal and growth polarity. At least some aspects of these systems seem to be widely conserved among eukaryotes; for example, the Cdc42 protein, which was first detected by analyzing yeast mutants defective in bud emergence, has a human homologue that is > 80% identical in amino acid sequence and appears to play a central role in cell cycle control and the spatial organization of human cells.

Second, we are exploring the structure and function of the novel cytoskeletal or protein-scaffolding system involving the septin family of proteins. The septins were first detected in budding yeast by analyzing mutants defective in the formation of a set of 10-nm filaments on the inner face of the plasma membrane that is necessary for proper bud growth, cytokinesis, and the placement of positional markers. However, it is now clear that the septins are present generally in other fungi and in animals (including humans) where they appear to play analogous roles in cell division and the control of cell-surface organization. It was our interest in the septins that drew us into work on Drosophila, where we can study the roles of these proteins in a genetically tractable animal system.

Third, our interest in the roles of the septins in cytokinesis has also drawn us into a broader interest in this process. Thus, we are now studying aspects of the assembly and function of the actomyosin contractile ring as well as the mechanisms by which cells position the cleavage plane properly relative to the orientation of the mitotic spindle and the positions of adjoining cells during development.

Publications
Bi, E., P. Maddox, D.J. Lew, E.D. Salmon, J. McMillan, E. Yeh & J.R. Pringle. Involvement of an actomyosin contractile ring in Saccharomyces cerevisiae cytokinesis. J. Cell Biol. 142: 1301-1312. 1998

Longtine, M.S., H. Fares & J.R. Pringle. Role of the yeast Gin4p protein kinase in septin assembly and the relationship between septin assembly and septin function. J. Cell Biol. 143: 719-736. 1998

Frazier, J.A., M.L. Wong, M.S. Longtine, J.R. Pringle, M. Mann, T.J. Mitchison & C. Field. Polymerization of purified yeast septins: evidence that organized filament arrays may not be required for septin function. J. Cell Biol. 143: 737-750. 1998

Rodrguez-Medina, J.R., J.A. Cruz, P.W. Robbins, E. Bi & J.R. Pringle. Elevated expression of chitinase 1 and chitin synthase in myosin II-deficient Saccharomyces cerevisiae. Cell. Mol. Biol. 44: 919-925. 1998

Longtine, M.S. & J.R. Pringle. Septins. In Guidebook to the Cytoskeletal and Motor Proteins (T. Kreis & R. Vale, eds.), in press. Oxford: Oxford University Press. 1998

E-mail: jpringle@email.unc.edu
Telephone: (919) 962-2293
FAX: (919) 962-1625
Address: Chapel Hill, NC

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