Biological Sciences Seminars
Role of Drosophila Light in endo-lysosomal trafficking
by Ms. Swetha MG, NCBS, Bangalore
Tuesday, September 13, 2011
from
to
(Asia/Kolkata)
at Colaba Campus ( B-333 )
at Colaba Campus ( B-333 )
Description |
Lysosomes are the primary degradative organelles of cells. In addition to regulating protein turnover, lysosomes are also involved in several other cellular processes such as modulation of signaling, antigen processing and plasma membrane repair. In metazoans, these lysosomes are characterized by a unique tubular morphology, acidic pH, and specific membrane protein (LAMP) and lipid (cholesterol) composition as well as a soluble protein (hydrolases) composition. Defects in lysosome formation and functioning have been long associated with several lysosome storage disorders as well as some multi-symptomatic syndromes such as Chediak Higashi syndrome and Hermansky Pudlak syndromes. Thus, identifying and characterizing molecules that are involved in lysosome biogenesis in a metazoan context is of importance. In Drosophila, a subset of genes called the "Granule group" of eye color genes affect the biogenesis of pigment granules, which are lysosome-related organelles. Several of these genes, such as garnet, deep orange (dor) and carnation, have also been shown to have a role in intracellular traffic. I have examined the role of the eye color gene, light, in endo-lysosomal trafficking. Perturbation of Light results in impaired lysosomal acidification, sterol accumulation, altered lysosomal morphology as well as compromised lysosomal degradation. I find that Drosophila Light regulates the fusion of a specific subset of biosynthetic carriers containing characteristic endolysosomal membrane proteins- LAMP1, V0-ATPase and the cholesterol transport protein, NPC1, with the endo-lysosomal system, and is then required for the morphological progression of the multivesicular endosome. Inhibition of Light results in accumulation of biosynthetic transport intermediates that contain these membrane cargo, whereas under similar conditions, endosomal delivery of soluble hydrolases (previously shown to be mediated by Dor), is not affected. Unlike Dor, Light is recruited to endosomes in a PI3P-sensitive fashion wherein it facilitates fusion of these biosynthetic cargo with the endosomes. Depletion of the mammalian counterpart of Light, hVps41, in a human cell line also inhibits delivery of hLAMP to endosomes, suggesting an evolutionarily conserved pathway in metazoa. |