Differential regulation of translation and endocytosis of alternatively spliced forms of the type II bone morphogenetic protein (BMP) receptor

Ayelet R. Amsalem, Barak Marom, Keren E. Shapira, Tal Hirschhorn, Livia Preisler, Pia Paarmann, Petra Knaus, Yoav I. Henis*, Marcelo Ehrlich

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The expression and function of transforming growth factor-β superfamily receptors are regulated by multiple molecular mechanisms. The type II BMP receptor (BMPRII) is expressed as two alternatively spliced forms, a long and a short form (BMPRII-LF and-SF, respectively), which differ by an ∼500 amino acid C-terminal extension, unique among TGF-β superfamily receptors. Whereas this extension was proposed to modulate BMPRII signaling output, its contribution to the regulation of receptor expression was not addressed. To map regulatory determinants of BMPRII expression, we compared synthesis, degradation, distribution, and endocytic trafficking of BMPRII isoforms and mutants. We identified translational regulation of BMPRII expression and the contribution of a 3′ terminal coding sequence to this process. BMPRII-LF and-SF differed also in their steady-state levels, kinetics of degradation, intracellular distribution, and internalization rates. A single dileucine signal in the C-terminal extension of BMPRII-LF accounted for its faster clathrin-mediated endocytosis relative to BMPRII-SF, accompanied by mildly faster degradation. Higher expression of BMPRII-SF at the plasma membrane resulted in enhanced activation of Smad signaling, stressing the potential importance of the multilayered regulation of BMPRII expression at the plasma membrane.

Original languageEnglish
Pages (from-to)716-730
Number of pages15
JournalMolecular Biology of the Cell
Volume27
Issue number4
DOIs
StatePublished - 15 Feb 2016

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