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Vol. 18, Issue 8, 2795-2804, August 2007

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A Developmentally Regulated Chaperone Complex for the Endoplasmic Reticulum of Male Haploid Germ Cells

Marcel van Lith^*, Anna-Riikka Karala, Dave Bown^*, John A. Gatehouse^*, Lloyd W. Ruddock, Philippa T.K. Saunders, and Adam M. Benham^*

*Department of Biological and Biomedical Sciences, University of Durham, Durham, DH1 3LE, United Kingdom; Biocenter Oulu and Department of Biochemistry, University of Oulu, 90014 Oulu, Finland; and Medical Research Council Human Reproductive Sciences Unit, The Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom

Submitted February 20, 2007; Revised April 23, 2007; Accepted May 4, 2007
Monitoring Editor: Sean Munro

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 -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.

Address correspondence to: Adam Benham (adam.benham{at}durham.ac.uk).

Abbreviations used: BPTI, bovine pancreatic trypsin inhibitor; endoH, endoglycosidase H; IAA, iodo-acetic acid; MHC, major histocompatibility complex; PDI, protein disulfide isomerase; PDILT, protein disulfide isomerase-like protein of the testis.