The Mechanism of Sperm/egg interaction and involved factors.

新合成的膜蛋白在内质网（ER）中的正确折叠是形成功能成熟蛋白所必需的。钙连接蛋白是一种普遍存在的内质网分子伴侣，通过保留不完全或错误折叠的蛋白质在质量控制中发挥重要作用。与其他已知的分子伴侣（Hsps、BiP和钙网蛋白）相比，钙连接蛋白是一种完整的膜蛋白。Calmegin是一种睾丸特异性ER蛋白，与Calnexin同源。我们在这里报告，钙调素结合新生的多肽在精子发生和钙调素的生理功能进行了分析，有针对性地破坏其基因。纯合子无效男性几乎不育，即使精子发生形态正常，交配正常。在体外，精子从纯合子无效男性没有坚持到卵细胞外基质（透明质酸），这种缺陷可能会解释观察到的不育。这些结果表明，钙调蛋白作为一个或多个精子表面蛋白，介导精卵相互作用的伴侣。钙调素缺陷小鼠精子的透明膜粘附缺陷表型使人联想到某些人类男性不明原因不育的病例。

The proper folding of newly synthesized membrane proteins in the endoplasmic reticulum (ER) is required for formation of functional mature proteins. Calnexin is a ubiquitous ER chaperone that plays afrnajor role in quality control by retaining incompletely or misfolded proteins. In contrast to other known chaperones (Hsps, BiP and calreticulin), calnexin is an integral membrane protein. Calmegin is a testis-specific ER protein that is homologous to calnexin. We report here that calmegin binds to nascent polypeptides during spermatogenesis and the physiological function of calmegin has been analyzed by targeted disruption of its gene. Homozygous null males were nearly sterile even though spermatogenesis was morphologically normal and mating was normal. In vitro, sperm from homozygous null males did not adhere to the egg extracellular matrix (zona pellucida), and this defect may explain the observed infertility. These results suggest that calmegin functions as a chaperone for one or more sperm surface proteins that mediate sperm-egg interactions. The defective zona pellucida adhesion phenotype of sperm from calmegin deficient mice is reminiscent of certain cases of human male unexplained infertility.