• PMID: 19457927
• Gene Name: AMHR2
• Condition: Persistent Mullerian duct syndrome
• Association: This shows that the AMHRII signal sequence is defective and suggests that AMHRII uses its transmembrane domain instead of its signal sequence to translocate to the endoplasmic reticulum, a characteristic of type III membrane proteins.
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Persistent Mullerian duct syndrome

Natural mutations of the anti-Mullerian hormone type II receptor found in persistent Mullerian duct syndrome affect ligand binding, signal transduction and cellular transport

Belville C, Maréchal JD, Pennetier S, Carmillo P, Masgrau L, Messika-Zeitoun L, Galey J, Machado G, Treton D, Gonzalès J, Picard JY, Josso N, Cate RL, di Clemente N.

The anti-Müllerian hormone type II (AMHRII) receptor is the primary receptor for anti-Müllerian hormone (AMH), a protein produced by Sertoli cells and responsible for the regression of the Müllerian duct in males. AMHRII is a membrane protein containing an N-terminal extracellular domain (ECD) that binds AMH, a transmembrane domain, and an intracellular domain with serine/threonine kinase activity. Mutations in the AMHRII gene lead to persistent Müllerian duct syndrome in human males. In this paper, we have investigated the effects of 10 AMHRII mutations, namely 4 mutations in the ECD and 6 in the intracellular domain. Molecular models of the extra- and intracellular domains are presented and provide insight into how the structure and function of eight of the mutant receptors, which are still expressed at the cell surface, are affected by their mutations. Interestingly, two soluble receptors truncated upstream of the transmembrane domain are not secreted, unless the transforming growth factor beta type II receptor signal sequence is substituted for the endogenous one. This shows that the AMHRII signal sequence is defective and suggests that AMHRII uses its transmembrane domain instead of its signal sequence to translocate to the endoplasmic reticulum, a characteristic of type III membrane proteins. FAU - Belville, Corinne AU - Belville C AD - INSERM U782, 32 rue des Carnets, Clamart F-92140, France. FAU - Maréchal, Jean-Didier AU - Maréchal JD FAU - Pennetier, Sophie AU - Pennetier S FAU - Carmillo, Paul AU - Carmillo P FAU - Masgrau, Laura AU - Masgrau L FAU - Messika-Zeitoun, Liza AU - Messika-Zeitoun L FAU - Galey, Julie AU - Galey J FAU - Machado, Gabrielle AU - Machado G FAU - Treton, Dominique AU - Treton D FAU - Gonzalès, Jacques AU - Gonzalès J FAU - Picard, Jean-Yves AU - Picard JY FAU - Josso, Nathalie AU - Josso N FAU - Cate, Richard L AU - Cate RL