Faure E, Gouédard L, Imbeaud S, Cate R, Picard J Y, Josso N, di Clemente N
Unité de Recherches sur l'Endocrinologie du Développement (INSERM), Ecole Normale Supérieure, Département de Biologie, 1 rue Maurice-Arnoux, 92120 Montrouge, France.
J Biol Chem. 1996 Nov 29;271(48):30571-5. doi: 10.1074/jbc.271.48.30571.
Anti-Müllerian hormone, a member of the transforming growth factor beta superfamily, produces early regression of Müllerian ducts in the male fetus through binding to a serine/threonine kinase receptor, homologous to type II receptors of the transforming growth factor beta (TGF-beta) family. A splice mutation of this receptor, described in a patient with abnormal retention of Müllerian derivatives, generates two mutant isoforms, one lacking the second exon and the other bearing an insertion of 12 bases between exons 2 and 3. Using hemagglutinin-tagged recombinant receptors, we have visualized wild type and mutant receptors in COS cells by Western blotting and immunoprecipitation. The 82-kDa, endoglycosidase H-insensitive, mature form of the wild type receptor is reduced to 68 kDa by N-glycosidase F treatment. Mutant receptor isoforms, 73 and 63 kDa for the long and short form, respectively, are sensitive to endoglycosidase H, suggesting that they are retained in the endoplasmic reticulum. Indeed, only the wild type receptor was expressed on the cell surface and bound iodinated anti-Müllerian hormone. These results provide a biological explanation for the failure of the mutant receptor to induce Müllerian regression.
抗苗勒管激素是转化生长因子β超家族的成员之一，它通过与一种丝氨酸/苏氨酸激酶受体结合，使雄性胎儿的苗勒管早期退化，该受体与转化生长因子β（TGF-β）家族的II型受体同源。在一名有苗勒管衍生物异常存留的患者中描述了这种受体的一种剪接突变，产生了两种突变异构体，一种缺少第二个外显子，另一种在外显子2和3之间有12个碱基的插入。使用带有血凝素标签的重组受体，我们通过蛋白质免疫印迹法和免疫沉淀法在COS细胞中观察到了野生型和突变型受体。野生型受体82 kDa、对内切糖苷酶H不敏感的成熟形式经N-糖苷酶F处理后降至68 kDa。长型和短型突变受体异构体分别为73 kDa和63 kDa，对内切糖苷酶H敏感，表明它们滞留在内质网中。实际上，只有野生型受体在细胞表面表达并结合碘化抗苗勒管激素。这些结果为突变受体未能诱导苗勒管退化提供了生物学解释。
