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The Drosophila Pigmentation Gene pink (p) Encodes a Homologue of Human Hermansky–Pudlak Syndrome 5 (HPS5)

Authors: David E. Krantz; Elizabeth S. Brooks; Juan M. Falcón-Pérez; Esteban C. Dell'Angelica; Rafael Romero-Calderón;

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.

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Keywords

Male, Sequence Homology, Amino Acid, Pigmentation, Molecular Sequence Data, Proteins, Nerve Tissue Proteins, Eye, Phenotype, Hermanski-Pudlak Syndrome, Mutation, Animals, Drosophila Proteins, Drosophila, Amino Acid Sequence, Carrier Proteins

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
38
Top 10%
Top 10%
Top 10%
bronze