Origin of the integrin-mediated signal transduction - Functional studies with cell cultures from the sponge Suberites domuncula

Sponges (phylum Porifera) represent the phylogenetically oldest metazoan an imals. Recently, from the marine sponge Geodia cydonium a first cDNA encodi ng a putative integrin receptor molecule was isolated. In the present study basic functional experiments have been conducted to test the hypothesis th at in sponges integrin polypeptides also function as adhesion molecules and as outside-in signaling molecules. The sponge Suberites domuncula has been used for the experiments because from this sponge only has a cell culture been established. Here we report that aggregation factor (AF)-mediated cell -cell adhesion is blocked by the RGDS peptide which is known to interact wi th beta integrin. Both RGDS and AF were found to stimulate DNA synthesis wi thin 24 h. The beta subunit of the integrin receptor was cloned from S, dom uncula: the estimated 91-kDa molecule comprises the characteristic signatur es. Evolutionary conservation of the beta integrin was assessed by comparis on with corresponding beta integrin subunits from evolutionary higher metaz oan taxa. Addition of RGDS or of AF to isolated cells of S. domuncula cause s a rapid (within 1-2 min) increase in the intracellular Ca2+ concentration which is further augmented in the presence of Ca2+. Furthermore, incubatio n of the cells with RGDS or AF causes an activation of the GTP-binding prot ein Pas. In addition it is shown that after a prolonged incubation of the c ells with RGDS and AF the expression of the genes coding for Pas and for ca lmodulin is upregulated These results suggest that the integrin receptor fu nctions in the sponge system not only as adhesion molecule but also as a mo lecule involved in outside-in signaling.