期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 7, 页码 2578-2583出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1319947111
关键词
endocytosis; receptor trafficking; C. elegans
资金
- National Institutes of Health [R01GM103995, R01GM67237]
- Busch Biomedical Grant
- Charles and Johanna Busch Predoctoral Fellowship
- National Science Foundation-Integrated Graduate Education and Research Traineeship [0801620]
- Direct For Education and Human Resources
- Division Of Graduate Education [0801620] Funding Source: National Science Foundation
The transforming growth factor beta (TGF beta) superfamily of signaling pathways, including the bone morphogenetic protein (BMP) subfamily of ligands and receptors, controls a myriad of developmental processes across metazoan biology. Transport of the receptors from the plasma membrane to endosomes has been proposed to promote TGF beta signal transduction and shape BMP-signaling gradients throughout development. However, how postendocytic trafficking of BMP receptors contributes to the regulation of signal transduction has remained enigmatic. Here we report that the intracellular domain of Caenorhabditis elegans BMP type I receptor SMA-6 (small-6) binds to the retromer complex, and in retromer mutants, SMA-6 is degraded because of its missorting to lysosomes. Surprisingly, we find that the type II BMP receptor, DAF-4 (dauer formation-defective-4), is retromer-independent and recycles via a distinct pathway mediated by ARF-6 (ADP-ribosylation factor-6). Importantly, we find that loss of retromer blocks BMP signaling in multiple tissues. Taken together, our results indicate a mechanism that separates the type I and type II receptors during receptor recycling, potentially terminating signaling while preserving both receptors for further rounds of activation.
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