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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/L871    most recent 00052.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sorokina, E. M. Articles by Fisher, A. B. PubMed PubMed Citation Articles by Sorokina, E. M. Articles by Fisher, A. B.

Identification of the amino acid sequence that targets peroxiredoxin 6 to lysosome-like structures of lung epithelial cells

Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Submitted 18 February 2009 ; accepted in final form 14 August 2009

Peroxiredoxin 6 (Prdx6), an enzyme with glutathione peroxidase and PLA₂ (aiPLA₂) activities, is highly expressed in respiratory epithelium, where it participates in phospholipid turnover and antioxidant defense. Prdx6 has been localized by immunocytochemistry and subcellular fractionation to acidic organelles (lung lamellar bodies and lysosomes) and cytosol. On the basis of their pH optima, we have postulated that protein subcellular localization determines the balance between the two activities of Prdx6. Using green fluorescent protein-labeled protein expression in alveolar epithelial cell lines, we showed Prdx6 localization to organellar structures resembling lamellar bodies in mouse lung epithelial (MLE-12) cells and lysosomes in A549 cells. Localization within lamellar bodies/lysosomes was in the luminal compartment. Targeting to lysosome-like organelles was abolished by the deletion of amino acids 31–40 from the Prdx6 NH₂-terminal region; deletion of the COOH-terminal region had no effect. A green fluorescent protein-labeled peptide containing only amino acids 31–40 showed lysosomal targeting that was abolished by mutation of S32 or G34 within the peptide. Studies with mutated protein indicated that lipid binding was not necessary for Prdx6 targeting. This peptide sequence has no homology to known organellar targeting motifs. These studies indicate that the localization of Prdx6 in acidic organelles and consequent PLA₂ activity depend on a novel 10-aa peptide located at positions 31–40 of the protein.

phospholipase A₂; lung lamellar bodies; lipid binding; protein targeting motif; lipase motif