Biology Reference
In-Depth Information
the movement of epithelial sheets. The sequence of molecular events that start
with adhesion of a cell to a surface or another cell and ends with cytoskeletal
activation remains to be defined fully. Dictyostelium discoideum is a lower
eukaryote that has been exploited in studies of chemotaxis, phagocytosis and
development due to its well characterized chemotactic and phagocytic
behaviours, simplicity of its developmental cycle, the ability to inactivate
genes either by design or randomly and the wide range of assays available for
analysing these mutants. Many of its behaviours can be readily manipulated in
the laboratory and it is possible to obtain suciently large quantities of cells
to enable the isolation and characterization of molecules involved in a process
of interest. The recent discovery of interesting new mutants with adhesion
defects that exhibit altered phagocytic, motility or developmental behaviours
has focused new attention on this system for the study of links between cell
surface receptors and the cytoskeleton.
Dictyostelium are highly motile and make close contact with the substratum
over a broad region during migration (Gingell et al., 1982; Weber et al., 1995).
This contrasts with the slower moving cultured cells that are more familiar to
cell biologists. Cells such as fibroblasts make smaller contacts with the
substratum, termed focal contacts while the cell is actively moving and focal
adhesions when the cell is stationary (Wehrle-Haller and Imhof, 2002). The
type of broad contact that Dictyostelium amoebae make with a substratum is
not unique to this cell type. Leukocytes, similarly highly motile cells, also
engage wide regions of substrate during movement indicating that this
mechanism of adhesion is perhaps better suited for relatively rapid migration
(Friedl et al., 2001). Studies in an easily manipulatable system such as
Dictyostelium should, therefore, provide general insights into how fast-moving
cells from a range of organisms make optimal contacts with the surface along
which they must move.
Dictyostelium amoebae are professional phagocytes and subsist on bacteria
in the wild. Depletion of this food supply initiates the developmental
programme that is characterized by a halt in cell division and expression of
genes required for chemotaxis (Loomis, 1982), such as the chemoattractant
receptor cAR1 and adenylyl cyclase (Devreotes, 1994). Cells begin to secrete
the chemoattractant cAMP and as one source of cAMP begins to predominate
cells migrate towards it via a signal-relay system. In addition to chemotaxis
genes, genes encoding cell adhesion molecules are also turned on in sequence
(Coates and Harwood, 2001). The cells begin to adhere to each other in a
head-to-tail fashion at the same time as a combination of calcium- and
magnesium-dependent cell-cell contacts are made (Loomis, 1982; Coates and
Harwood, 2001). Observation of aggregating cells reveals that the formation
of these contacts is preceded by the extension and interdigitation of filopodia
from one cell to another (Choi and Siu, 1987; Sesaki and Siu, 1996). Typically,
a total of 1610
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cells stream together to form a mound and during the later
