Constitutive negative regulation in the processing of the anti-Müllerian hormone receptor II
| Autor: | R. Blake Pepinsky, Nathalie di Clemente, Marcelo Ehrlich, Ayelet R. Amsalem, Jean Yves Picard, Nechama I. Smorodinsky, Tal Hirschhorn, Richard L. Cate |
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| Rok vydání: | 2015 |
| Předmět: |
Anti-Mullerian Hormone
Male Protein Folding medicine.medical_specialty Receptors Peptide Endocytic cycle Protein Serine-Threonine Kinases Biology Endoplasmic Reticulum Mice Transforming Growth Factor beta Internal medicine Anti-Müllerian hormone receptor Extracellular medicine Animals Humans Receptor Regulation of gene expression Endoplasmic reticulum Cell Membrane Receptor Transforming Growth Factor-beta Type II Cell Biology Transforming growth factor beta Protein Structure Tertiary Cell biology Endocrinology Gene Expression Regulation Hormone receptor biology.protein Protein Processing Post-Translational Receptors Transforming Growth Factor beta Protein Binding |
| Zdroj: | Journal of Cell Science. 128:1352-1364 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | The levels and intracellular localization of wild-type transforming growth factor β superfamily (TGFβ-SF) receptors are tightly regulated by endocytic trafficking, shedding and degradation. In contrast, a main regulatory mechanism of mutation-bearing receptors involves their intracellular retention. Anti-Müllerian hormone receptor II (AMHRII, also known as AMHR2) is the type-II receptor for anti-Müllerian hormone (AMH), a TGFβ-SF ligand that mediates Müllerian duct regression in males. Here, we studied AMHRII processing and identified novel mechanisms of its constitutive negative regulation. Immunoblot analysis revealed that a significant portion of AMHRII was missing most of its extracellular domain (ECD) and, although glycosylated, was unfolded and retained in the endoplasmic reticulum. Exogenous expression of AMHRII, but not of type-II TGF-β receptor (TβRII, also known as TGFR2), resulted in its disulfide-bond-mediated homo-oligomerization and intracellular retention, and in a decrease in its AMH-binding capacity. At the plasma membrane, AMHRII differed from TβRII, forming high levels of non-covalent homomeric complexes, which exhibited a clustered distribution and restricted lateral mobility. This study identifies novel mechanisms of negative regulation of a type-II TGFβ-SF receptor through cleavage, intracellular retention and/or promiscuous disulfide-bond mediated homo-oligomerization. |
| Databáze: | OpenAIRE |
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