Dictyostelium discoideum lipids modulate cell-cell cohesion and cyclic AMP signaling.

Abstract

During Dictyostelium discoideum development, cell-cell communication is mediated through cyclic AMP (cAMP)-induced cAMP synthesis and secretion (cAMP signaling) and cell-cell contact. Cell-cell contact elicits cAMP secretion and modulates the magnitude of a subsequent cAMP signaling response (D. R. Fontana and P. L. Price, Differentiation 41:184-192, 1989), demonstrating that cell-cell contact and cAMP signaling are not independent events. To identify components involved in the contact-mediated modulation of cAMP signaling, amoebal membranes were added to aggregation-competent amoebae in suspension. The membranes from aggregation-competent amoebae inhibited cAMP signaling at all concentrations tested, while the membranes from vegetative amoebae exhibited a concentration-dependent enhancement or inhibition of cAMP signaling. Membrane lipids inhibited cAMP signaling at all concentrations tested. The lipids abolished cAMP signaling by blocking cAMP-induced adenylyl cyclase activation. The membrane lipids also inhibited amoeba-amoeba cohesion at concentrations comparable to those which inhibited cAMP signaling. The phospholipids and neutral lipids decreased cohesion and inhibited the cAMP signaling response. The glycolipid/sulfolipid fraction enhanced cohesion and cAMP signaling. Caffeine, a known inhibitor of cAMP-induced adenylyl cyclase activation, inhibited amoeba-amoeba cohesion. These studies demonstrate that endogenous lipids are capable of modulating amoeba-amoeba cohesion and cAMP-induced activation of the adenylyl cyclase. These results suggest that cohesion may modulate cAMP-induced adenylyl cyclase activation. Because the complete elimination of cohesion is accompanied by the complete elimination of cAMP signaling, these results further suggest that cohesion may be necessary for cAMP-induced adenylyl cyclase activation in D. discoideum.The well-defined life cycle of Dictyostelium discoideum makes it an excellent model system in which to study the mechanisms through which extracellular signals regulate differentiation and morphogenesis. D. discoideum grows as an amoeboid cell in the presence of an adequate supply of its bacterial food source. Following starvation, approximately 105 amoebae aggregate into a mound. Subsequent stages of morphogenesis result in the formation of a pseudoplasmodium and then a fruiting body (for an overview of the life cycle, see reference 4).After the initiation of development, the acquisition of aggregation competence involves the synthesis of a cell surface cyclic AMP (cAMP) receptor (20), an increase in the rate of synthesis of a phosphodiesterase (22), and an increase in adenylyl cyclase activity (25). When amoebae are aggregation competent, cAMP binds to the surface cAMP receptor, causing a transient activation of the adenylyl cyclase and the subsequent secretion of cAMP (9). This response to extracellular cAMP is called cAMP signaling or cAMP relay. cAMP signaling and chemotaxis to cAMP result in the organized aggregation of amoebae into mounds (43).The mechanism of recep...

Regulation of spatiotemporal expression of cell–cell adhesion molecules during development of Dictyostelium discoideum

“…1992). Since the formation of cell–cell contacts affects cAMP metabolism and cAMP signaling (Fontana & Price 1988; Fontana et al. 1991a,b), it is possible that the loss of DdCAD‐1 expression may somehow enhance cAMP signaling and stimulate a higher level of csA/gp80 expression.…”

Molecular Cloning and Characterization of DdCAD-1, a Ca2+-dependent Cell-Cell Adhesion Molecule, in

“…In addition to intercellular adhesion, there is increasing evidence that the classic cadherins are involved in signal transduction (72). In Dictyostelium, several recent reports have shown that cell-cell contact can elicit cAMP secretion and modulate cAMP signaling in Dictyostelium (73)(74)(75). Recent studies in our laboratory have demonstrated a role for cell-cell contact in a cAMP-dependent pathway that regulates gene expression, as well as in the cAMP signal relay system (19).…”

Synthesis of the Ca2+-dependent cell adhesion molecule DdCAD-1 is regulated by multiple factors during Dictyostelium development

“…Several recent reports suggest that an interdependent relationship exists between cell-cell contact and cAMP signaling [15][16][17]. We have previously shown that cellcell contact is required for the stimulation of csaA expression [10].…”