title: Lysosomal sorting receptors are essential for secretory granule biogenesis in Tetrahymena.
abstract: Secretory granules, such as neuronal dense core vesicles, are specialized for storing cargo at high concentration and releasing it via regulated exocytosis in response to extracellular stimuli. Here, we used expression profiling to identify new components of the machinery for sorting proteins into mucocysts, secretory granule-like vesicles in the ciliate Tetrahymena thermophila. We show that assembly of mucocysts depends on proteins classically associated with lysosome biogenesis. In particular, the delivery of nonaggregated, but not aggregated, cargo proteins requires classical receptors of the sortilin/VPS10 family, which indicates that dual mechanisms are involved in sorting to this secretory compartment. In addition, sortilins are required for delivery of a key protease involved in T. thermophila mucocyst maturation. Our results suggest potential similarities in the formation of regulated secretory organelles between even very distantly related eukaryotes.
authors.affiliation: Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Briguglio
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Turkewitz
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D020869:Gene Expression Profiling; D008247:Lysosomes / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D016808:Tetrahymena thermophila / Q000378:metabolism* / Q000502:physiology; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D011506:Proteins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D000099183:Sortilin; C018589:lysosomal proteins