title: A developmentally regulated chaperone complex for the endoplasmic reticulum of male haploid germ cells.
abstract: Glycoprotein folding is mediated by lectin-like chaperones and protein disulfide isomerases (PDIs) in the endoplasmic reticulum. Calnexin and the PDI homologue ERp57 work together to help fold nascent polypeptides with glycans located toward the N-terminus of a protein, whereas PDI and BiP may engage proteins that lack glycans or have sugars toward the C-terminus. In this study, we show that the PDI homologue PDILT is expressed exclusively in postmeiotic male germ cells, in contrast to the ubiquitous expression of many other PDI family members in the testis. PDILT is induced during puberty and represents the first example of a PDI family member under developmental control. We find that PDILT is not active as an oxido-reductase, but interacts with the model peptide Delta-somatostatin and nonnative bovine pancreatic trypsin inhibitor in vitro, indicative of chaperone activity. In vivo, PDILT forms a tissue-specific chaperone complex with the calnexin homologue calmegin. The identification of a redox-inactive chaperone partnership defines a new system of testis-specific protein folding with implications for male fertility.
authors.affiliation: Department of Biological and Biomedical Sciences, University of Durham, Durham, DH1 3LE, United Kingdom.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Lith
authors.forename: Anna-Riikka
authors.initials: AR
authors.lastname: Karala
authors.forename: Dave
authors.initials: D
authors.lastname: Bown
authors.forename: John A
authors.initials: JA
authors.lastname: Gatehouse
authors.forename: Lloyd W
authors.initials: LW
authors.lastname: Ruddock
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
authors.forename: Adam M
authors.initials: AM
authors.lastname: Benham
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D055592:Biophysical Phenomena; D001703:Biophysics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006238:Haploidy; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013094:Spermatozoa / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D018832:Molecular Chaperones; D011134:Polysaccharides; C087341:calmegin; C496702:PDILT protein, human; D019704:Protein Disulfide-Isomerases