title: Deficiency in lysosomal enzyme secretion is associated with upregulation of phosphatidylinositol 4-phosphate in tetrahymena.
abstract: A variety of lower eukaryotes and certain mammalian cells are known to constitutively secrete lysosomal hydrolases. Recent studies in Tetrahymena have shown that phosphatidylinositol 3-phosphate regulates the proper secretion of lysosomal enzymes at the level of phagolysosome formation. We extend these findings by studying the secretion-deficient strain MS-1 of Tetrahymena thermophila, which possess phosphatidylinositol levels similar to wild type. However, steady-state levels of phosphatidylinositol 4-phosphate (PtdIns4P) were found to be doubled in this strain compared with wild type as shown by in vivo [3H]inositol labeling and high-performance liquid chromatography analysis. The increased PtdIns4P levels in MS-1 cells were unrelated to the upregulation of total phosphatidylinositol phosphate induced by hyperosmotic stress because this treatment resulted in a similar increase of PtdIns4P in MS-1 and wild-type cells. Hyperosmotic stress did not affect secretion in either of the two types of cells. On the other hand, under conditions of wortmannin-induced hypersecretion in wild-type cells, MS-1 cells developed a highly vacuolated phenotype while secretion was not induced. Importantly, comparative analysis of wild-type and MS-1 cells under wortmannin treatment showed that PtdIns4P levels were differentially regulated in the two strains. These results collectively suggest that PtdIns4P turnover in Tetrahymena is linked to lysosome secretion.
authors.affiliation: Laboratory of Biochemistry, Department of Chemistry, University of Athens, Zografou, 15771 Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Deli
authors.forename: George
authors.initials: G
authors.lastname: Leondaritis
authors.forename: Arno
authors.initials: A
authors.lastname: Tiedtke
authors.forename: Dia
authors.initials: D
authors.lastname: Galanopoulou
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002855:Chromatography, Thin Layer; D008247:Lysosomes / Q000201:enzymology*; D009154:Mutation; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D013768:Tetrahymena / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018129:Phosphatidylinositol Phosphates; D010726:Phosphodiesterase Inhibitors; C055525:phosphatidylinositol 3-phosphate; C037178:phosphatidylinositol 4-phosphate; D000135:Acid Phosphatase; D010738:Type C Phospholipases; D000077191:Wortmannin