title: Natural mutations of the anti-Mullerian hormone type II receptor found in persistent Mullerian duct syndrome affect ligand binding, signal transduction and cellular transport.
abstract: 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.
authors.affiliation: INSERM U782, 32 rue des Carnets, Clamart F-92140, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Belville
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Maréchal
authors.forename: Sophie
authors.initials: S
authors.lastname: Pennetier
authors.forename: Paul
authors.initials: P
authors.lastname: Carmillo
authors.forename: Laura
authors.initials: L
authors.lastname: Masgrau
authors.forename: Liza
authors.initials: L
authors.lastname: Messika-Zeitoun
authors.forename: Julie
authors.initials: J
authors.lastname: Galey
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Machado
authors.forename: Dominique
authors.initials: D
authors.lastname: Treton
authors.forename: Jacques
authors.initials: J
authors.lastname: Gonzalès
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Picard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Josso
authors.forename: Richard L
authors.initials: RL
authors.lastname: Cate
authors.forename: Nathalie
authors.initials: N
authors.lastname: di Clemente
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D012734:Disorders of Sex Development / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D018000:Receptors, Peptide / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D008024:Ligands; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone