FUNCTIONS OF THE CYTOPLASMIC DOMAIN OF THE BETA(PS) INTEGRIN SUBUNIT DURING DROSOPHILA DEVELOPMENT

Integrins constitute a family of membrane-spanning, heterodimeric prot eins that mediate adhesive interactions between cells and surrounding extracellular matrices (or other cells) and participate in signal tran sduction. We are interested in assessing integrin functions in the con text of developing Drosophila melanogaster. This report, using mutants of the beta(PS) subunit encoded by the myospheroid (mys) locus, analy zes the relationships between integrin protein structure and developme ntal functions in an intact organism. As a first step in this analysis , we demonstrated the ability of a fragment of wild-type mys genomic D NA, introduced into the germ line in a P-element vector P[mys(+)], to rescue phenotypes attributed to lack of (or defects in) the endogenous beta(PS) during several discrete morphogenetic events. We then produc ed in vitro a series of modifications of the wild-type P[mys(+)] trans poson, which encode beta(PS) derivatives with mutations within the sma ll and highly conserved cytoplasmic domain. In vivo analysis of these mutant transposons led to the following conclusions. (1) The cytoplasm ic tail of beta(PS) is essential for all developmental functions of th e protein that were assayed. (2) An intron at a conserved position in the DNA sequence encoding the cytoplasmic tail is thought to participa te in important alternative splicing events in vertebrate beta integri n subunit genes, but is not required for the developmental functions o f the mys gene assayed here. (3) Phosphorylation on two conserved tyro sines found in the C terminus of the beta(PS) cytoplasmic tail is not necessary for the tested developmental functions. (4) Four highly cons erved amino acid residues found in the N-terminal portion of the cytop lasmic tail are important but not critical for the developmental funct ions of beta(PS); furthermore, the efficiencies with which these mutan t proteins function during different morphogenetic processes vary grea tly, strongly suggesting that the cytoplasmic interactions involving P S integrins are developmentally modulated.