title: The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5).
abstract: Lysosome-related organelles comprise a group of specialized intracellular compartments that include melanosomes and platelet dense granules (in mammals) and eye pigment granules (in insects). In humans, the biogenesis of these organelles is defective in genetic disorders collectively known as Hermansky-Pudlak syndrome (HPS). Patients with HPS-2, and two murine HPS models, carry mutations in genes encoding subunits of adaptor protein (AP)-3. Other genes mutated in rodent models include those encoding VPS33A and Rab38. Orthologs of all of these genes in Drosophila melanogaster belong to the 'granule group' of eye pigmentation genes. Other genes associated with HPS encode subunits of three complexes of unknown function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2 and -3, for which the Drosophila counterparts had not been characterized. Here, we report that the gene encoding the Drosophila ortholog of the HPS5 subunit of BLOC-2 is identical to the granule group gene pink (p), which was first studied in 1910 but had not been identified at the molecular level. The phenotype of pink mutants was exacerbated by mutations in AP-3 subunits or in the orthologs of VPS33A and Rab38. These results validate D. melanogaster as a genetic model to study the function of the BLOCs.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Falcón-Pérez
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero-Calderón
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Brooks
authors.forename: David E
authors.initials: DE
authors.lastname: Krantz
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Dell'Angelica
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D005123:Eye / Q000378:metabolism; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D010641:Phenotype; D010858:Pigmentation / Q000235:genetics*; D011506:Proteins; D017386:Sequence Homology, Amino Acid
chemical_list: C104378:BLOC1S1 protein, human; C492647:BLOC1S2 protein, human; C509457:BLOC1S3 protein, human; D002352:Carrier Proteins; D029721:Drosophila Proteins; C493900:HPS5 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins