Identification, expression pattern, and characterization of mouse glutaredoxin 2 isoforms.
Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase involved in the maintenance of mitochondrial redox homeostasis. Grx2 was first characterized as mitochondrial protein, but alternative mRNA variants lacking the transit peptide-encoding first exon were demonstrated for human and proposed for mouse. We systematically screened for alternative transcript variants of mouse Grx2. We identified a total of six exons, three constitutive (II, III, and IV), two alternative first exons (exons Ia and Ic), and one single-cassette exon (exon IIIb) located between exons III and IV. Exons Ic and IIIb are not present in the human genome; mice lack human exon Ib. The six exons give rise to five transcript variants that encode three protein isoforms: mitochondrial Grx2a, a cytosolic isoform that is homologous to the cytosolic/nuclear human Grx2c and present in specific cells of many tissues and the testis-specific isoform Grx2d that is unique to mice. Mouse Grx2c can form an iron/sulfur cluster-bridged dimer, is enzymatically active as a monomer, and can donate electrons to ribonucleotide reductase. Testicular cells lack mitochondrial Grx2a but contain cytosolic Grx2. Prominent immunostaining was detected in spermatogonia and spermatids. These results provide evidence for additional functions of Grx2 in the cytosol, in cell proliferation, and in cellular differentiation.
Hudemann
Christoph
C
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Lönn
Maria Elisabet
ME
Godoy
José Rodrigo
JR
Zahedi Avval
Farnaz
F
Capani
Francisco
F
Holmgren
Arne
A
Lillig
Christopher Horst
CH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D005091:Exons; D020224:Expressed Sequence Tags; D015870:Gene Expression; D054477:Glutaredoxins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016366:Open Reading Frames; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013087:Spermatids / Q000378:metabolism; D013093:Spermatogonia / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D018076:DNA, Complementary; D004220:Disulfides; C516009:Glrx2 protein, mouse; D054477:Glutaredoxins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins