The Drosophila NCAM homolog Fas2 signals independent of adhesion

Abstract

The development of tissues and organs requires close interaction of cells. To do so, cells express adhesion proteins such as the neural cell adhesion molecule (NCAM) or its Drosophila orthologue Fasciclin 2 (Fas2). Both are members of the Ig-domain superfamily of proteins that mediate homophilic adhesion. These proteins are expressed as different isoforms differing in their membrane anchorage and their cytoplasmic domains. To study the function of single isoforms we have conducted a comprehensive genetic analysis of fas2. We reveal the expression pattern of all major Fas2 isoforms, two of which are GPI-anchored. The remaining five isoforms carry transmembrane domains with variable cytoplasmic tails. We generated fas2 mutants expressing only single isoforms. In contrast to the null mutation which causes embryonic lethality, these mutants are viable, indicating redundancy among the different isoforms. Cell type specific rescue experiments showed that glial secreted Fas2 can rescue the fas2 mutant phenotype to viability. This demonstrates cytoplasmic Fas2 domains have no apparent essential functions and indicate that Fas2 has function(s) other than homophilic adhesion. In conclusion, our data propose novel mechanistic aspects of a long studied adhesion protein.