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Serine 32 to threonine mutation preserves peroxiredoxin 6 structure and enzymatic function but abolishes its trafficking to lamellar bodies in vivo
Author(s) -
Sorokina Elena,
Dodia Chandra,
Tao JianQin,
Zhou Suiping,
Feinstein Sheldon,
Fisher Aron
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.565.4
Subject(s) - lamellar granule , pulmonary surfactant , chemistry , microbiology and biotechnology , dipalmitoylphosphatidylcholine , peroxiredoxin , biochemistry , phospholipid , phosphatidylcholine , biology , enzyme , peroxidase , membrane
Peroxiredoxin 6 (Prdx6), a bifunctional protein with lysosomal‐type phospholipase A 2 (aiPLA 2 ) and GSH peroxidase activities, protects lungs from oxidative stress and participates in lung surfactant phospholipid (PL) turnover. Prdx6 has been localized to both cytosol and acidic organelles (lamellar bodies [LB] and lysosomes) in lung epithelium and its organellar targeting sequence has been identified ( 31 DSWGILFSHP 40 , Am.J.Physiol.297 : L871, 2009). Interestingly, an S32T mutation fully preserved secondary structure of recombinant protein and had no effect on either its peroxidase or aiPLA 2 activity. In a “knock‐in” mouse model carrying the S32T mutation in the Prdx6 gene, Prdx6 protein and aiPLA 2 activity were present in lung epithelial cells. However,the protein was absent from epithelial cell LB. Lung surfactant dipalmitoylphosphatidylcholine (DPPC) is endocytosed by alveolar epithelial cells and degraded by aiPLA2. The content of total phospholipid, PC, and disaturated phosphatidylcholine (DSPC) in bronchoalveolar lavage fluid, lung lamellar bodies, and lung homogenate was increased in S32T mutant animals and degradation of internalized [ 3 H]DPPC in isolated mouse lungs was significantly decreased. Thus, Thr can substitute for Ser for the enzymatic activities of Prdx6 but not for its targeting to LB. These results confirm an important role for lamellar body Prdx6 in the degradation and remodeling of lung surfactant phosphatidylcholine. [HL‐019737, HL102016 and HL105509]