Spermatocyte/spermatid-specific thioredoxin-3, a novel Golgi apparatus-associated thioredoxin, is a specific marker of aberrant spermatogenesis.
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.
Jiménez
Alberto
A
Center for Biotechnology, Department of Biosciences at NOVUM, Karolinska Institutet, S-14157 Huddinge, Sweden.
Zu
Wei
W
Rawe
Vanesa Y
VY
Pelto-Huikko
Markku
M
Flickinger
Charles J
CJ
Sutovsky
Peter
P
Gustafsson
Jan-Ake
JA
Oko
Richard
R
Miranda-Vizuete
Antonio
A
D020101:Acrosome Reaction; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism; D005434:Flow Cytometry; D015723:Gene Library; D014644:Genetic Variation; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013087:Spermatids / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism*; D013091:Spermatogenesis; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection
D018076:DNA, Complementary; D012333:RNA, Messenger; C490377:TXNDC8 protein, human; D013879:Thioredoxins