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Originally published In Press as doi:10.1074/jbc.M404192200 on June 4, 2004

J. Biol. Chem., Vol. 279, Issue 33, 34971-34982, August 13, 2004
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Spermatocyte/Spermatid-specific Thioredoxin-3, a Novel Golgi Apparatus-associated Thioredoxin, Is a Specific Marker of Aberrant Spermatogenesis*

Alberto Jiménez,ab Wei Zu,c Vanesa Y. Rawe,d Markku Pelto-Huikko,ef Charles J. Flickinger,gh Peter Sutovsky,ij Jan-Åke Gustafsson,a Richard Oko,ck and Antonio Miranda-Vizueteal

From the aCenter for Biotechnology, Department of Biosciences at NOVUM, Karolinska Institutet, S-14157 Huddinge, Sweden, cDepartment of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada, dPittsburgh Development Center, Magee-Womens Research Institute, Departments of Obstetrics, Gynecology, and Reproductive Sciences, and Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, eDepartment of Developmental Biology, Tampere University Medical School and Department of Pathology, Tampere University Hospital, Fin-33101 Tampere, Finland, gDepartment of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, and iDepartments of Animal Science and Obstetrics & Gynecology, University of Missouri-Columbia, Columbia, Missouri 65211-5300

Mammalian germ cells are endowed with a complete set of thioredoxins (Trx), a class of redox proteins located in specific structures of the spermatid and sperm tail. We report here the characterization, under normal and pathological conditions, of a novel thioredoxin with a germ line-restricted expression pattern, named spermatocyte/spermatid-specific thioredoxin-3 (SPTRX-3). The human SPTRX-3 gene maps at 9q32, only 50 kb downstream from the TRX-1 gene from which it probably originated as genomic duplication. Therefore, human SPTRX-3 protein comprises a unique thioredoxin domain displaying high homology with the ubiquitously expressed TRX-1. Among the tissues investigated, Sptrx-3 mRNA is found exclusively in the male germ cells at pachytene spermatocyte and round spermatid stages. Light and electron microscopy show SPTRX-3 protein to be predominately located in the Golgi apparatus of pachytene spermatocytes and round and elongated spermatids, with a transient localization in the developing acrosome of round spermatids. In addition, increased levels of SPTRX-3, possibly caused by overexpression, are observed in morphologically abnormal human spermatozoa from infertile men. In addition, SPTRX-3 is identified as a novel postobstruction autoantigen. In this report, we propose that SPTRX-3 can be used as a specific marker for diverse sperm and testis pathologies. SPTRX-3 is the first thioredoxin specific to the Golgi apparatus, and its function within this organelle might be related to the post-translational modification of proteins required for germ cell-specific functions, such as acrosomal biogenesis.


Received for publication, April 15, 2004 , and in revised form, May 28, 2004.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF305830, AY495589, and AY496270.

* This work was supported in part by Swedish Medical Research Council Projects 03P-14096, 03X-14041, and 13X-10370 and grants from the Åke Wibergs Stiftelse and the Karolinska Institutet (to A. M.-V.). We acknowledge the generous support of the Reproductive Sciences for the Americas Network (RSANET) (to V. Y .R.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–5 and Tables I and II.

b Supported by postdoctoral fellowship EX2003-0390 from the Spanish Ministerio de Educacion, Cultura y Deporte.

f Supported by the Medical Research Fund of Tampere University Hospital.

h Supported by NIDDK Grant P50-DK45179 and NICHD Grant HD-U54-29009, National Institutes of Health.

j Supported by the Food for the 21st Century Program of the University of Missouri-Columbia and by United States Department of Agriculture/National Research Initiative Grant 2002-02069.

k Supported by Canadian grants from the Natural Sciences and Engineering Research Council of Canada and Canadian Institutes of Health Research.

l To whom correspondence should be addressed. Tel.: 46-8-6083375; Fax: 46-8-7745538; E-mail: anmi{at}biosci.ki.se.


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