Journal Article

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

Corinne Belville, Jean-Didier Maréchal, Sophie Pennetier, Paul Carmillo, Laura Masgrau, Liza Messika-Zeitoun, Julie Galey, Gabrielle Machado, Dominique Treton, Jacques Gonzalès, Jean-Yves Picard, Nathalie Josso, Richard L. Cate and Nathalie di Clemente

in Human Molecular Genetics

Volume 18, issue 16, pages 3002-3013
Published in print August 2009 | ISSN: 0964-6906
Published online May 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp238
Natural mutations of the anti-Müllerian hormone type II receptor found in persistent Müllerian duct syndrome affect ligand binding, signal transduction and cellular transport

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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.

Journal Article.  7989 words.  Illustrated.

Subjects: Genetics and Genomics

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