期刊
JOURNAL OF CELL SCIENCE
卷 118, 期 16, 页码 3663-3673出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02502
关键词
endocytic trafficking; Vps-C genes; pigment granules; lysosome-related organelles; autophagosomes
类别
资金
- NEI NIH HHS [R01 EY010199, EY 10199] Funding Source: Medline
- NINDS NIH HHS [NS43406] Funding Source: Medline
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.
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