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Haploid specific calreticulin homologue, calspelin, is required for sperm fertility

机译：单倍体特异性钙网蛋白同源物，钙蛋白，是精子受精所必需的

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The proper folding of nascent polypeptides in endoplasmic reticulum (ER) is crucial to make functional membrane proteins. Ubiquitously expressed ER resident proteins calnexin and calreticulin function in concert as lectin chaperones and play a major role in quality control of glycoproteins maturation. In the testis, besides these chaperones, we previously reported that calmegin functions as calnexin like chaperone and required for sperm fertility. Although crt2/calr3 (we termed here as calspelin) has been cloned as testicular homologue of calreticulin, the physiological functions remained to be unknown. Here we show that calspelin is a male haploid germ cell specific protein homologous to somatic ER chaperone, calreticulin. When we produced calspelin -/- animals, homologous mutant males were healthy but infertile. They produced normal looking sperm but the sperm migration into oviduct and the sperm zona pellucida binding were impaired as observed in calmegin -/- mice. Further study revealed that calspelin -/- mouse sperm present ADAMlb and ADAM2 but ADAM3, while calmegin -/- mouse sperm lack all. With the fact that the loss of zona binding was commonly observed in ADAM3 -/- mice, we suggest that calpelin is required for ADAM3 maturation and subsequent sperm fertility.
机译：新生多肽在内质网（ER）中的正确折叠对于制造功能性膜蛋白至关重要。遍在表达的ER驻留蛋白calnexin和Calreticulin协同起凝集素伴侣的作用，并在糖蛋白成熟的质量控制中起主要作用。在睾丸中，除这些伴侣蛋白外，我们先前还报道过降钙素像伴侣蛋白一样起钙连蛋白的作用，是精子受精所必需的。尽管已将crt2 / calr3（我们在这里称为calspelin）克隆为钙网蛋白的睾丸同源物，但其生理功能仍然未知。在这里，我们显示钙蛋白是一种雄性单倍体生殖细胞特异性蛋白，与体细胞ER伴侣钙网蛋白同源。当我们生产calspelin-/-动物时，同源突变的雄性是健康的但不育。他们产生正常外观的精子，但如在Calegin-/-小鼠中观察到的那样，精子向输卵管的迁移和精子透明带的结合受到损害。进一步的研究表明，降钙素-/-小鼠精子中存在ADAM1b和ADAM2，而ADAM3却没有，而降钙素-/-小鼠精子中的所有精子都缺乏。鉴于在ADAM3-/-小鼠中普遍观察到透明带结合力的丧失，我们建议钙蛋白是ADAM3成熟和随后精子受精所必需的。

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