Calsperin Is a Testis-specific Chaperone Required for Sperm Fertility
Calsperin Is a Testis-specific Chaperone Required for Sperm Fertility
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DOI：
10.1074/jbc.m110.140152
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发表时间：
2011-02-18
影响因子：
4.8
通讯作者：
Okabe, Masaru
中科院分区：
文献类型：
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作者：
Ikawa, Masahito;Tokuhiro, Keizo;Okabe, Masaru
钙连接蛋白（CANX）和钙网蛋白（CALR）是位于内质网中的同源凝集素伴侣，并共同介导新生糖蛋白折叠。在睾丸中，钙调蛋白（CLGN）和钙调蛋白（CALR 3）分别表达为CANX和CALR的生殖细胞特异性对应物。在这里，我们表明，Calr 3（-/-）男性产生明显正常的精子，但不育，因为有缺陷的精子从子宫迁移到输卵管和有缺陷的结合透明质酸。而CLGN所需的ADAM 1A/ADAM 2二聚体和随后的成熟的ADAM 3，精子膜蛋白受精所需的，我们表明，CALR 3是一个凝集素缺乏的伴侣蛋白直接需要ADAM 3成熟。我们的研究结果确立了CALR 3的客户特异性，并表明生殖细胞特异性CALR样内质网伴侣在男性生育力的发展中具有对比功能。关键精子蛋白成熟机制的识别和理解将为避孕和治疗原因不明的男性不育症的新方法铺平道路。
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.