Constitutive negative regulation in the processing of the anti-Müllerian hormone receptor II

Tal Hirschhorn, Nathalie di Clemente, Ayelet R. Amsalem, R. Blake Pepinsky, Jean Yves Picard, Nechama I. Smorodinsky, Richard L. Cate*, Marcelo Ehrlich

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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 homooligomerization 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.

Original languageEnglish
Pages (from-to)1352-1364
Number of pages13
JournalJournal of Cell Science
Issue number7
StatePublished - 2015


  • Anti-Müllerian hormone
  • Disulfide bonds
  • Fluorescence recovery after photobleaching
  • Immunofluorescence co-patching
  • Receptor
  • Receptor oligomerization
  • TGF-β superfamily


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