Defective pigment granule biogenesis and aberrant behavior caused by mutations in the Drosophila AP-3 beta adaptin gene ruby

Lysosomal protein trafficking is a fundamental process conserved from yeast to humans. This conservation extends to lysosome-like organelles such as m ammalian melanosomes and insect eye pigment granules. Recently, eye and coa t color mutations in mouse (mocha and pearl) and Drosophila (garnet and car mine) were shown to affect subunits of the heterotetrameric adaptor protein complex AP-3 involved in vesicle trafficking. Here we demonstrate that the Drosophila eye color mutant ruby is defective in the AP-3 beta subunit gen e. ruby expression was found in retinal pigment and photoreceptor cells and in the developing central nervous system, entry mutations lead to a decrea sed number and altered size of pigment granules in various cell types in an d adjacent to the retina. Humans with lesions in die related AP-3 beta A ge ne suffer from Hermansky-Pudlak syndrome, which is caused by defects in a n umber of lysosome-related organelles. Hermansky-Pudlak patients have a redu ced skin pigmentation and suffer from internal bleeding, pulmonary fibrosis , and visual system malfunction. The Drosophila AP-3 beta adaptin also appe ars to be involved in precesses other than eye pigment granule biogenesis b ecause all ruby allele combinations tested exhibited defective behavior in a visual fixation paradigm.