title: Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules.
abstract: Mutations that disrupt trafficking to lysosomes and lysosome-related organelles cause multiple diseases, including Hermansky-Pudlak syndrome. The Drosophila eye is a model system for analyzing such mutations. The eye-color genes carnation and deep orange encode two subunits of the Vps-C protein complex required for endosomal trafficking and pigment-granule biogenesis. Here we demonstrate that dVps16A (CG8454) encodes another Vps-C subunit. Biochemical experiments revealed a specific interaction between the dVps16A C-terminus and the Sec1/Munc18 homolog Carnation but not its closest homolog, dVps33B. Instead, dVps33B interacted with a related protein, dVps16B (CG18112). Deep orange bound both Vps16 homologs. Like a deep orange null mutation, eye-specific RNAi-induced knockdown of dVps16A inhibited lysosomal delivery of internalized ligands and interfered with biogenesis of pigment granules. Ubiquitous knockdown of dVps16A was lethal. Together, these findings demonstrate that Drosophila Vps16A is essential for lysosomal trafficking. Furthermore, metazoans have two types of Vps-C complexes with non-redundant functions.
authors.affiliation: Center for Basic Neuroscience, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9111, USA.
authors.forename: Suprabha
authors.initials: S
authors.lastname: Pulipparacharuvil
authors.forename: Mohammed Ali
authors.initials: MA
authors.lastname: Akbar
authors.forename: Sanchali
authors.initials: S
authors.lastname: Ray
authors.forename: Evgueny A
authors.initials: EA
authors.lastname: Sevrioukov
authors.forename: Adam S
authors.initials: AS
authors.lastname: Haberman
authors.forename: Jack
authors.initials: J
authors.lastname: Rohrer
authors.forename: Helmut
authors.initials: H
authors.lastname: Krämer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004331:Drosophila melanogaster; D011992:Endosomes / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D010860:Pigments, Biological / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D034622:RNA Interference; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C104790:DOR protein, Drosophila; D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D010860:Pigments, Biological; D011506:Proteins; C507251:VPS16A protein, Drosophila; C411584:VPS33B protein, human; D033921:Vesicular Transport Proteins; C400361:car protein, Drosophila