Interaction with protein phosphatase 1 is essential for bifocal function during the morphogenesis of the Drosophila compound eye

The gene bifocal (bif), required for photoreceptor morphogenesis in the Dro sophila compound eye, encodes a protein that is shown to interact with prot ein phosphatase 1 (PP1) using the yeast two-hybrid system. Complex formatio n between Bif and PPI is supported by coprecipitation of the two proteins. Residues 992 to 995 (RVQF) in the carboxy-terminal region of Bif, which con form to the consensus PPI-binding motif, are shown to be essential for the interaction of Bif with PPI. The interaction of PP1 with bacterially expres sed and endogenous Bif can be disrupted by a synthetic peptide known to blo ck interaction of other regulatory subunits with PPI. Null bif mutants exhi bit a rough eye phenotype, disorganized rhabdomeres (light-gathering rhodop sin-rich microvillar membrane structures in the photoreceptor cells) and al terations in the actin cytoskeleton. Expression of wild-type bif transgenes resulted in significant rescue of these abnormalities. In contrast, expres sion of transgenes encoding the Bif F995A mutant, which disrupts binding to PP1, was unable to rescue any aspect of the bif phenotype. The results ind icate that the PP1-Bif interaction is critical for the rescue and that a ma jor function of Bif is to target PP1c to a specific subcellular location. T he role of the PP1-Bif complex in modulating the organization of the actin cytoskeleton underlying the rhabdomeres is discussed.