Rong Li, Ph.D.

Research Interests

I. Establishment of cell polarity
Most cells – from lymphocytes to neurons to yeast – are polarized, and their polarity is central to such processes as cell migration and organ function, yet we do not understand the origin of cell polarity in any system. The budding yeast presents an excellent model for understanding the molecular pathway and fundamental mechanisms that lead to the establishment of cell polarity. We have been combining biochemical and genetic analysis to answer these three questions: 1) Which protein factors play critical roles in the assembly of actin filaments? 2) How are these actin assembly factors regulated by the Cdc42 small GTPase? 3) How do Cdc42 activation and actin polymerization lead to the establishment of cell polarity?

Specific research goals are:
1) We will try to understand, at a mechanistic level, the role of type-I myosin motor in the regulation of actin dynamics .
2) We are involved in a program project using a combined genetic and structural approach to understand the regulation and mechanism of Arp2/3 complex-based actin nucleation.
3) We will further investigate how vesicular transport and recycling play roles in the regulation of the Cdc42 small GTPase. We think that our findings could be general to other Rho-family GTPases.
4) We will use a combination of mathematical modeling and genetic tests to understand the coupling between cue-dependent signaling and the intrinsic cytoskeleton-based mechanism during cell polarity establishment.

II. Cytokinesis
Cytokinesis – the physical division of a cell into two - is a fascinating example of coordinated cell behavior, where the cytoskeleton, membrane and cell cycle regulatory machinery must function together to allow large scale physical rearrangements on a time scale of seconds to minutes. Our initial contribution to this field was the discovery that cytokinesis in budding yeast involves an actomyosin-based contractile ring. This finding provides an opportunity to use the budding yeast as a model to study contractile ring assembly and regulation.

Current research goals are:
1) We will continue to elucidate the process of actomyosin ring assembly at a biochemical level.
2) To understand the regulation of cytokinesis onset, we will attempt to identify the structural targets of the mitotic exit network.
3) We recently showed that targeted exocytosis is required for cytokinesis in yeast, as shown in animal cells. This finding allows us to take advantage of the large amount of knowledge and reagents generated in the yeast vesicular trafficking field to understand how membrane is inserted at the site of cell division.

III. Cell motility and morphogenesis
We have also initiated projects that are aimed at understanding how the basic machines involved in cell polarization, motility and division are regulated during the generation of diverse cell types that constitute metazoan organisms.

A spreading 3T3 fibroblast.
Shown in green is phalloidin staining of actin structures,
in red localization of the Arp2/3 complex.

A yeast cell during mitosis.
Shown in green localization of the mitotic checkpoint
protein Bfa1at the spindle pole body, in red the mitotic spindle,
and in blue the nuclear DNA.

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Recent Publications

Li, R. (1999) Bifurcation of the mitotic checkpoint pathway in yeast. Proc. Natl. Acad. Sci., USA. 96:4989-4994.

Winter D., Lechler, T. and Li, R. (1999) Activation of the yeast Arp2/3 complex by Bee1p, a WASP family protein. Curr. Biol. 9:501-504.

Winter, D. C., Chau, E. C., and Li, R. (1999) Genetic dissection of the yeast Arp2/3 complex: a comparison of the in vivo and structural roles of individual subunits. Proc. Natl. Acad. Sci., USA. 96:7288-7293.

Field, C., Li, R., and Oegema, K. (1999) Cytokinesis in eukaryotes: a mechanistic comparison. Curr. Opin. Cell Biol. 11, 66-80.

Lechler, T., Shevchenko A., Shevchenko A., and Li R. (2000) Direct involvement of yeast type I myosins in Cdc42-dependent actin polymerization. J. Cell Biol. 148:363-

Shannon, K. and Li, R. (2000) A myosin light chain mediates the localization of the budding yeast IQGAP-like protein during contractile ring formation. Curr. Biol. 10:727-730

Lippincott, J. and Li, R. (2000) Nuclear envelope fission is linked to cytokinesis in budding yeast. Exp. Cell Res. 260:277-83.

Lippincott, J. and Li, R. (2000) PCH, a conserved protein family that play diverse roles during cytokinesis. Microscopy Res. Techniques. 49:168-172

Li R. (2000) Mitosis: shut the door behind when you leave. Curr. Biol. 10:R781-R784.

Lippincott, J., Shannon, K., Shou,W., Deshaies, R. J., and Li, R. The Tem1 Small GTPase Controls Actomyosin and Septin Dynamics during Cytokinesis. J. Cell Sci. 2001; 114:1379-1386.

Volkmann, N, Amann, K.J., Stoilova-McPhie, S., Egile, C., Winter, D.C., Hazelwood, L., Heuser, J.E., Li, R., Pollard, T.D., and Hanein, D. Structure of Arp2/3 Complex in Its Activated State and in Actin Filament Branch Junctions. Science. 2001; 293:2456-2459.

Lechler, T., Jonsdottir, G. A., Klee, S. K., Pellman, D., and Li, R. A two-tiered mechanism by which Cdc42 controls the localization and activation of an Arp2/3-activating motor complex in yeast. J. Cell Biol. 2001; 155:261-270.

Tolliday, N., Bouquin, N. and Li, R. Assembly and regulation of the cytokinetic apparatus in budding yeast. Curr. Opin. Microbiol. 2001; 4:690-695.

Soulard, A., Lechler, T., Spiridonov, V., Schevchenko, A., Li, R., and Winsor, B. Lsb7p is implicated with type I myosins in yeast actin patches polarization and is able to recruit actin polymerizing machinery in vitro. Mol. Cell Biol. 2002; 22:7889-7906.

Tolliday N., VerPlank, L., and Li, R. Rho1 directs formin-mediated actin ring assembly during budding yeast cytokinesis. Curr. Biol. 2002; 12:1864-1870.

Tolliday N, and Li, R. Direct evidence for a critical role of myosin-II in budding yeast cytokinesis and the evolvability of new cytokinetic mechanisms in the absence of myosin-II. Mol. Biol. Cell. 2003; 14:798-809.

Wedlich-Soldner, R., Altschuler, S., Wu, L., and Li, R. Spontaneous cell polarization through actomyosin-based delivery of the Cdc42 GTPase. Science 2003; 299:1231-1235.

Kreishman-Deitrick M, Egile C, Hoyt DW, Ford JJ, Li R, and Rosen MK. NMR Analysis of Methyl Groups in the 240kDa Arp2/3 Complex and Model Systems up to 560kDa. Biochemistry. 2003; 42:8579-8586

Wedlich-Soldner,R. and Li, R. Spontaneous cell polarization: Undermining determinism. Nat. Cell Biol. 2003;5:267-270