RRC ID 45973
Author Gleason RJ, Akintobi AM, Grant BD, Padgett RW.
Title BMP signaling requires retromer-dependent recycling of the type I receptor.
Journal Proc Natl Acad Sci U S A
Abstract The transforming growth factor β (TGFβ) 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 TGFβ 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.
Volume 111(7)
Pages 2578-83
Published 2014-2-18
DOI 10.1073/pnas.1319947111
PII 1319947111
PMID 24550286
PMC PMC3932876
MeSH Animals Animals, Genetically Modified Bone Morphogenetic Protein Receptors, Type I / metabolism* Bone Morphogenetic Proteins / metabolism* Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Microscopy, Fluorescence Multiprotein Complexes / genetics Multiprotein Complexes / metabolism* Real-Time Polymerase Chain Reaction Receptors, Cell Surface / metabolism* Receptors, Transforming Growth Factor beta / metabolism* Recombinant Fusion Proteins / metabolism Signal Transduction / genetics Signal Transduction / physiology*
IF 9.412
Times Cited 40
C.elegans tm1595 tm1447 tm5356 tm847