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Updated: Feb 18, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
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Membrane targeting of inhibitory Smads through palmitoylation controls TGF-β/BMP signaling

Wenqing Li1,2, Weini Li1,3, Lihui Zou2

  • 1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, 100101 Beijing, People's Republic of China.

Proceedings of the National Academy of Sciences of the United States of America
|November 29, 2017
PubMed

TGF-β/BMP (bone morphogenetic protein) signaling pathways play conserved roles in controlling embryonic development, tissue homeostasis, and stem cell regulation. Inhibitory Smads (I-Smads) have been shown to negatively regulate TGF-β/BMP signaling by primarily targeting the type I receptors for ubiquitination and turnover. However, little is known about how I-Smads access the membrane to execute their functions. Here we show that Dad, the Drosophila I-Smad, associates with the cellular membrane via palmitoylation, thereby targeting the BMP type I receptor for ubiquitination. By performing systematic biochemistry assays, we characterized the specific cysteine (Cys556) essential for Dad palmitoylation and membrane association. Moreover, we demonstrate that dHIP14, a Drosophila palmitoyl acyl-transferase, catalyzes Dad palmitoylation, thereby inhibiting efficient BMP signaling. Thus, our findings uncover a modification of the inhibitory Smads that controls TGF-β/BMP signaling activity.

Keywords:
DadDrosophila germ-line stem cellinhibitory Smadspalmitoylation

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