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Publication : Calsperin is a testis-specific chaperone required for sperm fertility.

First Author  Ikawa M Year  2011
Journal  J Biol Chem Volume  286
Issue  7 Pages  5639-46
PubMed ID  21131354 Mgi Jnum  J:170595
Mgi Id  MGI:4946942 Doi  10.1074/jbc.M110.140152
Citation  Ikawa M, et al. (2011) Calsperin is a testis-specific chaperone required for sperm fertility. J Biol Chem 286(7):5639-46
abstractText  Calnexin (CANX) and calreticulin (CALR) are homologous lectin chaperones located in the endoplasmic reticulum and cooperate to mediate nascent glycoprotein folding. In the testis, calmegin (CLGN) and calsperin (CALR3) are expressed as germ cell-specific counterparts of CANX and CALR, respectively. Here, we show that Calr3(-/-) males produced apparently normal sperm but were infertile because of defective sperm migration from the uterus into the oviduct and defective binding to the zona pellucida. Whereas CLGN was required for ADAM1A/ADAM2 dimerization and subsequent maturation of ADAM3, a sperm membrane protein required for fertilization, we show that CALR3 is a lectin-deficient chaperone directly required for ADAM3 maturation. Our results establish the client specificity of CALR3 and demonstrate that the germ cell-specific CALR-like endoplasmic reticulum chaperones have contrasting functions in the development of male fertility. The identification and understanding of the maturation mechanisms of key sperm proteins will pave the way toward novel approaches for both contraception and treatment of unexplained male infertility.
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