Arturo De Lozanne's Lab

Section of Molecular, Cell & Developmental Biology

University of Texas at Austin 

Arturo De Lozanne, Ph.D.
Associate Professor

Section of Molecular, Cell & Developmental Biology

241 Patterson Building
Campus Mail Code C-0930
University of Texas
Austin, TX 78712
Telephone (512) 232-6100

Molecular Genetic Analysis of Cytokinesis:

Cell movement is a process that is essential for all aspects of life. Cells display many types of movement: from the amoeba crawling in search of food to the neuron sending out a long axon to connect with a specific target cell. We are interested in the study of cell motility and its role in different aspects of cell biology. Our current efforts are directed towards understanding the molecular basis of cytokinesis.

The last step of the cell cycle, cytokinesis, is very poorly understood. What are the components of the contractile ring that divides a mitotic cell into two daughter cells? How does the cell determine the timing and location at which the contractile ring is assembled? To answer these questions we are using a combination of molecular genetic and biochemical techniques and we apply these to the unicellular organism
Dictyostelium discoideum. This organism undergoes cell division in a manner similar to mammalian cells, yet it is much easier to manipulate at the genetic level. We have generated a collection of cytokinesis mutants that will define important proteins involved in this process.

One of our mutants has a specific defect in a novel small GTPase which we have called
racE. This protein belongs to the rho & rac family of proteins that are known to regulate the actin cytoskeleton in mammalian cells. RacE-null cells fail in cytokinesis by regression of the cleavage furrow (Gerald et al., 1998). This regression is probably produced by a weakly organized actin cytoskeleton as evidenced by the profuse blebbing of racE-null cells undergoing cell division. We are actively engaged in determining how this important regulatory protein controls the distribution of the actomyosin cytoskeleton in response to the cell cycle.

Another mutant has a defect in a protein, called
lvsA, that is similar to a novel class of mammalian signaling proteins. This class includes the mouse beige and its human ortholog, the Chediak-Higashi Syndrome protein. The lvsA mutant cells fail in cytokinesis very differently from our racE-null cells. After forming a normal cleavage furrow, the cells develop a large 'bulge' in the middle of their furrows and cytokinesis fails. Intriguingly, this phenotype is similar to that of the clathrin-null cells, another cytokinesis-defective mutant (Niswonger, M. and O'Halloran, T.J.,1997,P.N.A.S. 94:8575-8578). Thus, based on the phenotype the lvsA mutants and sequence similarities of the lvsA protein, we postulate that lvsA is involved in a novel membrane processing pathway that is essential for cytokinesis.

The De Lozanne Lab: Lab Phone Number (512) 471-0862

Silvana Pavia Vila (Research Technician)

Juhi Yajnik (Graduate Student - Cell & Molecular Biology Graduate Program)

Hui Li (Graduate Student - Micobiology Graduate Program)

Qian Chen (Graduate Student - Cell & Molecular Biology Graduate Program)

Elena Kypri (Graduate Student - Micobiology Graduate Program)

William Marshall Guy (Undergraduate Student)

Kristin Zarzour (Undergraduate Student)

Current Publications

Wu, W., Yajnik, J., Siano, M., and De Lozanne, A. (2004) Structure-Function Analysis of the BEACH Protein LvsA. Traffic, 5: 346-355 [PDF file] [QuickTime Movies]

De Lozanne, A. (2003) The Role of BEACH Proteins in Dictyostelium. Traffic, 4: 6-12 [PDF file]

Wang, N., Wu, W., and De Lozanne, A. (2002) The BEACH Family of Proteins: Phylogenetic and Functional Analysis of Six Dictyostelium BEACH proteins. J. Cell. Biochem, 86: 561-570 [PDF file]

Harris, E., Wang, N., Wu, W., Weatherford, A., De Lozanne, A. and Cardelli, J. (2002) Dictyostelium LvsB Mutants Model the Lysosomal Defects Associated with Chediak-Higashi Syndrome. Mol. Biol. Cell, 13: 656-669 [PDF file]

Cornillon, S., Dubois, A., Brückert, F., Lefkir, Y., Marchetti, A., Benghezal, M., De Lozanne, A., Letourneur, F. and Cosson, F. (2002) Two members of the beige/CHS (BEACH) family are involved at different stages in the organization of the endocytic pathway in Dictyostelium. J. Cell Sci., 115: 737-744 [PDF file]

Gerald, N. J., Siano, M. and De Lozanne, A. (2002) The Dictyostelium LvsA Protein is Localized on the Contractile Vacuole and is Required for Osmoregulation. Traffic 3: 50-60 [QuickTime Movies] [PDF file]

Gerald, N. J., Damer, C.K., O'Halloran, T.J. and De Lozanne, A. (2001) Cytokinesis Failure in Clathrin-Minus Cells is Caused by Cleavage Furrow Instability. Cell Motil. Cytoskleton. 48: 213-223. [PDF file]

Larochelle, D.A., Gerald, N., and De Lozanne, A. (2000) Molecular Analysis of racE Function in Dictyostelium. Microsc. Res. Tech. 49: 145-151. [PDF file]

Kwak, E., Gerald, N., Larochelle, D.A., Vithalani, K.K., Niswonger, M.L., Maready, M., and De Lozanne, A. (1999) LvsA, a protein related to the mouse beige, is essential for cytokinesis in Dictyostelium. Mol. Biol. Cell, 10:4429-4439. [QuickTime Movies] [PDF file]

Vithalani, K.K., Parent, C., Thorn, E.M., Penn, M., Larochelle, D.A., Devreotes, P.N. and De Lozanne, A. (1998) Identification of Darlin, a Dictyostelium Protein with Armadillo-like Repeats that Binds to Small GTPases and is Important for the Proper Aggregation of Developing Cells. Mol. Biol. Cell, 9: 3095-3106 [PDF file]

Gerald, N., Dai, J., Ting-Beall, H. P. and De Lozanne, A. (1998) A role for Dictyostelium racE in cortical tension and cleavage furrow progression. J. Cell Biol. 141: 483-492. [PDF file] [QuickTime Movies]

Larochelle, D. A., Vithalani, K. and De Lozanne, A. (1997) The role of Dictyostelium racE in cytokinesis: mutational analysis and localization studies by use of green fluorescent protein. Mol. Biol. Cell, 8: 935-944. [Medline abstract]

Larochelle, D. A., Vithalani, K. and De Lozanne, A. (1996) A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis. J. Cell Biol., 133: 1321-1329. [Medline abstract] [PDF file 1 Mb]

Vithalani, K., Shoffner, J. D. and De Lozanne, A. (1996) Isolation and characterization of a novel cytokinesis-deficient mutant in Dictyostelium discoideum. J. Cell. Biochem., 62: 290-301. [Medline abstract] [PDF file]

Shoffner, J. D. and De Lozanne, A. (1996) Sequences in the myosin II tail required for self-association. Biochem. Biophys. Res. Commun. 218: 860-864. [Medline abstract]

Burns, C. G., Reedy, M., Heuser, J. and De Lozanne, A. (1995) Expression of light meromyosin in Dictyostelium blocks normal myosin II function. J. Cell Biol. 130: 605-612. [Medline abstract]

Burns, C. G., Larochelle, D. A., Erickson, H., Reedy, M. and De Lozanne, A. (1995) Single-headed myosin II acts as a dominant-negative mutation in Dictyostelium. Proc. Natl. Acad. Sci. USA., 92: 8244-8248. [Medline abstract] [PDF file 1 Mb]

Fukui, Y., De Lozanne, A. and Spudich, J. A. (1990) Structure and function of the cytoskeleton of a Dictyostelium myosin defective mutant. J. Cell Biol. 110: 367-378. [Medline abstract]

: De Lozanne, A. (1989). Gene targeting and cell motility. Cell Motil. Cytoskeleton 14: 62-68. [Medline citation]


CYTOFISSION IN RacE-Null mutants


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Last updated June, 2004