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Title: Membrane Targeting of Inhibitory Smads Through Palmitoylation Controls TGF-β/BMP Signaling
Author: Wenqing Li, Weini Li, Lihui Zou, Shanming Ji, Chaoyi Li, Kehui Liu, Guoqiang Zhang, Qinmiao Sun, Fei Xiao, Dahua Chen
Abstract: 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.
Corresponding author: Qinmiao Sun, Fei Xiao, Dahua Chen
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PubYear: 2017
Volume: 114
Issue: 50
Page: 13206-13211
Journal: PNAS
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URL: http://www.pnas.org/content/114/50/13206.full
   

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