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
E-mail: a.delozanneREMOVENOSPAM@mail.utexas.edu
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)
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]
Review: De Lozanne, A. (1989). Gene targeting and cell motility.
Cell Motil. Cytoskeleton 14: 62-68. [Medline
citation]
MOVIES:
Course Materials:
Last updated June, 2004