Signal transduction, cell differentiation, and genomics of Dictyostelium discoideum
One long-term goal of our laboratory is to define the cellular regulatory mechanisms that govern cell
differentiation in eukaryotes using Dictyostelium discoideum as a model. Dictyostelium cells normally live as solitary
amoebae in the soil, consuming other microbes by phagocytosis. Upon starvation, ~50,000 cells aggregate into a mound and
become an integrated multicellular organism with distinct tissue types. Each organism consists of about 70% prespore cells
and 30% prestalk cells. When conditions are favorable, they form a fruiting body, the terminal developmental structure that
is made up of a sorus of dormant spores held aloft on a cellular stalk. This system can be used to provide a complete picture
of the regulation of a significant biological problem: the integration of individual cells into a multicellular tissue with
the proper form and function. Previously, we had studied two ABC transporters, RhT and TagA, that operate very early in
development and which control aspects of initial cell differentiation. We have also characterized several components of the
regulatory network that governs the growth to development transition itself: a novel putative receptor/kinase GdtB, a
conserved protein kinase YakA and a conserved translational regulator PufA. These five regulators form critical links in the
regulatory network that controls growth, the decision to initiate development and initial establishment of specific cell
types- regulation that is common to all eukaryotes that undergo development. The function of these signaling pathways in
Dictyostelium are being studied by genetic, physiological and genomic methods.
Dictyostelium genomics:
Functional genomics holds the promise that we can define most of the significant functions of cells and organisms by
using genome-scale techniques to obtain a global view of biological systems. Genomics approaches will provide a unique
perspective of biological regulation by completing the "parts lists" for cellular functions and by outlining connections
between regulatory systems that could not be obtained by other methods. Before we can fully exploit this information we must
identify the genes, understand how the genes function and integrate this information into a comprehensive biological picture.
We are involved in the international effort to sequence the 34 Mb genome of Dictyostelium together with the Genome Sequencing
Center here. We are also planning to generate mutations in about 5,000 genes and phenotype the resulting strains using a
variety of traditional and genomic methods. This work will allow us to make testable predictions of gene function and to
propose regulatory networks. We are interested in those aspects of Dictyostelium biology that are common to all eukaryotic
organisms, and that will be informative for defining both the function of individual genes and the organization of regulatory
hierarchies that operate in development. The relative simplicity and genetic tractability of organisms such as Dictyostelium
should prove to be advantageous for genomic analyses of multicellular development.
Selected Publications
Wang B, Kuspa A (1997) Dictyostelium development in the absence of cAMP. Science
277:251-254.
Souza GM, Lu S, Kuspa A (1998) YakA, a protein kinase required for the transition from growth to
development in Dictyostelium. Development 125:2291-2302.
Souza GM, da Silva AM, Kuspa A (1999) Starvation promotes Dictyostelium development by relieving
PufA inhibition of PKA translation through the YakA kinase pathway. Development 126:3263-3274.
Wang B, Shaulsky G, Kuspa A (1999) Multiple developmental roles for CRAC, a cytosolic regulator
of adenylyl cyclase. Developmental Biology 208:1-13.
Good JR, Kuspa A (2000) Evidence that a cell-type-specific efflux pump regulates cell
differentiation in Dictyostelium. Developmental Biology 220:53-61.
Sucgang R, Shaulsky G, Kuspa A (2000) Toward the functional analysis of the Dictyostelium
discoideum genome. Journal of Eukaryotic Microbiology 47:334-339.
Wang B, Kuspa A (2002) CulB, a putative ubiquitin ligase subunit, regulates prestalk cell
differentiation and morphogenesis in Dictyostelium spp. Eukaryotic Cell 1:126-136.
Good JR, Cabral M, Sharma S, Yang J, Van Driessche N, Shaw CA, Shaulsky G, Kuspa A (2003) TagA,
a putative serine protease/ABC transporter of Dictyostelium that is required for cell fate
determination at the onset of development. Development 130:2953-2965.
Contact Information
- Adam Kuspa, Ph.D.
- Department of Biochemistry and Molecular Biology
- Baylor College of Medicine
- One Baylor Plaza T321
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-8278
- Fax: (713) 798-9438
- E-mail: akuspa@bcm.tmc.edu
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