Action Mechanism of Basigin, a Membrane Glycoprotein Belonging to the Immunoglobulin Superfamily

免疫球蛋白超家族膜糖蛋白Basigin的作用机制

• 批准号: 11670114
• 负责人: KADOMATSU Kenji
• 金额: $ 2.3万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670114/
• 关键词: basigin; immunoglobulin superfamily; spermatogenesis; homo-oligomer; retina; knockout mice; 無精子症; セルトリ細胞

Basigin (Bsg) is a membrane glycoprotein, which belongs to the immunoglobulin (Ig) superfamily. Bsg has two Ig-like domain in its extracellular portion. Bsg knockout mice manifested 1. many embryonic death during implantation, 2. death due to interstitial pneumonia within one month after birth, 3. failure of spermatogenesis, oocyte maturation and implantation and 4. learning and memory deficiency. Objective of this study is to elucidate 1. the role of Bsg in spermatogenesis, 2. the mechanism and biological meanings of the homo-oligomer formation of Bsg and 3. possibility of cross-talk between Bsg and embigin, a membrane glycoprotein that has a homology with Bsg.Bsg-deficient mice exhibited azoospermia with cessation of spermatogenesis at metaphase of the first meiosis. Unusual ectoplasmic specification between Sertoli cells and spermatids was detected in Bsg-deficient mice, suggesting involvement of Bsg in ectoplasmic specification. Homo-oligomer formation of Bsg took place in the same cell membrane (cis-type association). In this oligomer formation, the N-terminal Ig-like domain plays a critical role. No association was detected between Bsg and embigin.Further analyses of Bsg-deficient mice revealed a retinal dysfunction, in which both rod and cone photoreceptor cells were functionally, severely affected from early age. The photoreceptor cells then degenerated gradually and were almost ablated by 41 weeks. Strong Bsg expression was detected in the pigment epithelium.In summary, this study has revealed a mechanism of homo-oligomer formation, which may be important for Bsg action, and discovered a novel target tissue, namely the retina, where Bsg play an important role. Identification of intracellular binding proteins of Bsg and Bsg receptor is needed for further elucidation of Bsg action mechanism.

Basigin （Bsg）是一种膜糖蛋白，属于免疫球蛋白（Ig）超家族。Bsg在细胞外部分有两个类似igg的结构域。Bsg敲除小鼠表现为1。1 .植入过程中胚胎死亡较多；2 .出生后1个月内因间质性肺炎死亡；精子发生、卵母细胞成熟和着床失败；学习和记忆缺陷。本研究的目的是阐明1；Bsg在精子发生中的作用；Bsg和3同聚物形成的机理和生物学意义。Bsg与embigin（一种与Bsg同源的膜糖蛋白）之间可能存在串扰。bsg缺陷小鼠在第一次减数分裂中期精子发生停止，表现为无精子症。在Bsg缺陷小鼠中检测到支持细胞和精子之间异常的外质规格，提示Bsg参与外质规格。Bsg的同质寡聚物形成发生在同一细胞膜上（顺式结合）。在这种低聚物的形成中，n端Ig-like结构域起着关键作用。Bsg与血凝素之间没有关联。对bsg缺陷小鼠的进一步分析显示视网膜功能障碍，其中杆状和锥状感光细胞在幼年时就受到严重影响。41周后，感光细胞逐渐退化，基本消融。在色素上皮中检测到强Bsg表达。综上所述，本研究揭示了可能对Bsg起重要作用的同质寡聚物形成机制，并发现了Bsg在视网膜中发挥重要作用的新靶组织。为了进一步阐明Bsg的作用机制，需要鉴定Bsg和Bsg受体的胞内结合蛋白。

项目成果

Toyama,Y.ら: "Histological characterization of defective spermatogenesis in mice lacking the basigin."Anat.Histol.Embryol.. 28. 205-213 (1999)

Toyama, Y. 等人：“缺乏基础蛋白的小鼠精子发生缺陷的组织学特征。Anat.Histol.Embryol.. 28. 205-213 (1999)

Toyama, Y., Maekawa, M., Kadomatsu, K., Miyauchi, T., Muramatsu, T., Yuasa, S.: "Histological characterization of defective spermatogenesis in mice lacking the basigin."Anat.Histol.Embryol. 28. 205-213 (1999)

Toyama, Y.、Maekawa, M.、Kadomatsu, K.、Miyauchi, T.、Muramatsu, T.、Yuasa, S.：“缺乏基础蛋白的小鼠精子发生缺陷的组织学特征。”Anat.Histol.Embryol。

Hori, K., Katayama, N., Kachi, S., Kondo, M., Kadomatsu, K., Usukura, J., Muramatsu, T., Mori, S., Miyake, Y.: "Retinal dysfunction in basigin deficiency"Invest.Ophtalmol.Vis.Sci.. 41. 3128-3133 (2000)

Hori, K.、Katayama, N.、Kachi, S.、Kondo, M.、Kadomatsu, K.、Usukura, J.、Muramatsu, T.、Mori, S.、Miyake, Y.：“basigin 中的视网膜功能障碍

Tachikui, H., Kurosawa, N., Kadomatsu, K., Muramatsu, K.: "Genomic organization and promoter activity of embigin, a member of the immunoglobulin superfamily."Gene. 240. 325-332 (1999)

Tachikui，H.，Kurosawa，N.，Kadomatsu，K.，Muramatsu，K.：“免疫球蛋白超家族成员 embigin 的基因组组织和启动子活性。”基因。

Hori,Kenji: "Retinal dysfunction in basigin deficiency."Investigative Ophtalmology & Visual Science. 41・10. 3128-3133 (2000)

Hori, Kenji：“basigin 缺乏导致的视网膜功能障碍。”调查眼科与视觉科学 41・10（2000）。