SYNTHESIS OF THE CA2-DEPENDENT CELL-ADHESION MOLECULE DDCAD-1 IS REGULATED BY MULTIPLE FACTORS DURING DICTYOSTELIUM DEVELOPMENT()

In Dictyostelium discoideum, the cadA gene encodes the cell adhesion m olecule DdCAD-1, a protein of M-r 24,000, which mediates Ca2+-dependen t cell-cell adhesion during development. We have examined the effects of cAMP, cell-cell contact, and growth conditions on cadA expression, cadA has a unique pattern of expression, which appears to be a combina tion of the expression patterns of early genes and aggregation-stage g enes. Expression of the cadA gene in bacterially grown cells is activa ted at the beginning of the developmental cycle, followed by a period of rapid DdCAD-1 accumulation. The mRNA level reaches its maximum at 9 h of development and then declines to the basal level at similar to 1 8 h, while the protein level remains constant after reaching its maxim um at 12 h. Pulse-chase experiments have demonstrated that DdCAD-1 has a significantly longer half-life than the average cellular protein. T ranscription of the cadA gene is stimulated by exogenous cAMP pulses, leading to a 3- to 5-fold increase in the transcription rate. In the f gdA mutant, which lacks a functional G alpha 2, cAMP fails to enhance cadA expression, suggesting that cAMP stimulates cadA transcription vi a a G protein-dependent pathway. However, inhibition of cell-cell cont act has no effect on the synthesis of DdCAD-1. Growth conditions also have a major influence on cadA expression. Axenically grown cells prod uce a high level of cadA transcripts during vegetative growth. The mRN A level shows a steady decrease during development and is reduced to t he basal level by 12 h. In contrast, the level of DdCAD-1 remains rela tively high throughout development, suggesting that axenic growth affe cts the accumulation of cadA mRNA but not the stability of the protein . These results indicate that multiple mechanisms are involved to main tain a high level of DdCAD-1 during development.