The Mechanism of Sperm/egg interaction and involved factors.

精子/卵子相互作用的机制及相关因素。

• 批准号: 09480246
• 负责人: OKABE Masaru
• 金额: $ 5.89万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480246/
• 关键词: molecular chaperone; homologous recombination; fertilization; calmegin; 実験動物; 凍結保存

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.

新合成的膜蛋白在内质网（ER）中适当折叠是形成功能性成熟蛋白的必要条件。钙连蛋白是一种普遍存在的内质网伴侣，通过保留不完全或错误折叠的蛋白质在质量控制中起重要作用。与其他已知的伴侣蛋白（热休克蛋白，BiP和钙网蛋白）相比，钙连蛋白是一种完整的膜蛋白。钙连蛋白是睾丸特异性内质网蛋白，与钙连蛋白同源。我们在此报道，在精子发生过程中，钙蛋白与新生多肽结合，并通过靶向破坏其基因来分析钙蛋白的生理功能。即使精子发生和交配在形态上是正常的，纯合子的无雄性几乎是不育的。在体外，纯合子不育雄性的精子不粘附在卵细胞外基质（透明带）上，这一缺陷可能解释了所观察到的不育。这些结果表明，钙蛋白作为一种或多种精子表面蛋白的伴侣，介导精子与卵子的相互作用。钙蛋白缺乏小鼠精子的透明带粘连表型缺陷使人联想到人类男性不明原因不育的某些病例。

项目成果

Okabe,M.et al.: "Male infertility and the genetics of spermatogenesis[In Process Citation]" Am J Hum Genet. 62. 1274-1281 (1998)

Okabe,M.et al.：“男性不育和精子发生的遗传学[引用中]”Am J Hum Genet。

Ikawa,M.et al.: "The putative chaperone calmegin is required for sperm fertility." Nature. 387. 607-611 (1997)

Ikawa,M.等人：“精子的生育能力需要假定的伴侣钙镁蛋白。”

伊川 正人, 岡部 勝: "緑色に光るトランスジェニックマウス-新規マーカーGFPの応用" 細胞工学. 16. 581-587 (1997)

Masato Ikawa、Masaru Okabe：“发出绿光的转基因小鼠 - 新型标记 GFP 的应用”《细胞工程》16. 581-587 (1997)。

M.Ikawa, I.Wada, K.Kominaml, D.Watanabe, K.Toshimori, Y.Nishimune, and M.Okabe :"The putative chaperone calmegin is required for sperm fertility." Nature. 387. 607-11 (1997)

M.Ikawa、I.Wada、K.Kominaml、D.Watanabe、K.Toshimori、Y.Nishimune 和 M.Okabe：“假定的伴侣钙镁蛋白是精子生育能力所必需的。”

M.Okabe, M.Ikawa and J.Ashkenas :"Male Infertility and the Genetics of Spermatogenesis." Am.J.hum.Genet.62. 1274-81 (1998)

M.Okabe、M.Ikawa 和 J.Ashkenas：“男性不育和精子发生的遗传学”。