A juxtamembrane basolateral targeting motif regulates signaling through a TGF-β pathway receptor in Drosophila

Aidan J. Peterson, Stephen J. Murphy, Melinda G. Mundt, Mary Jane Shimell, Edward B. Leof, Michael B. O’Connor

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


In polarized epithelial cells, receptor–ligand interactions can: be restricted by different spatial distributions of the 2 interacting components, giving rise to an underappreciated layer of regulatory complexity. We explored whether such regulation occurs in the Drosophila wing disc, an epithelial tissue featuring the TGF-β family member Decapentaplegic (Dpp) as a morphogen controlling growth and patterning. Dpp protein has been observed in an extracellular gradient within the columnar cell layer of the disc, but also uniformly in the disc lumen, leading to the question of how graded signaling is achieved in the face of 2 distinctly localized ligand pools. We find the Dpp Type II receptor Punt, but not the Type I receptor Tkv, is enriched at the basolateral membrane and depleted at the junctions and apical surface. Wit, a second Type II receptor, shows a markedly different behavior, with the protein detected on all membrane regions but enriched at the apical side. Mutational studies identified a short juxtamembrane sequence required for basolateral restriction of Punt in both wing discs and mammalian Madin-Darby canine kidney (MDCK) cells. This basolateral targeting (BLT) determinant can dominantly confer basolateral localization on an otherwise apical receptor. Rescue of punt mutants with transgenes altered in the targeting motif showed that flies expressing apicalized Punt due to the lack of a functional BLT displayed developmental defects, female sterility, and significant lethality. We also show that apicalized Punt does not produce an ectopic signal, indicating that the apical pool of Dpp is not a significant signaling source even when presented with Punt. Instead, we find that basolateral presentation of Punt is required for optimal signaling. Finally, we present evidence that the BLT acts through polarized sorting machinery that differs between types of epithelia. This suggests a code whereby each epithelial cell type may differentially traffic common receptors to enable distinctive responses to spatially localized pools of extracellular ligands.

Original languageEnglish (US)
Article numbere3001660
JournalPLoS biology
Issue number5
StatePublished - May 2022

Bibliographical note

Funding Information:
MBO was funded by grant R35GM118029 for the National Institute of General Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Guillermo Marqués for the Punt-GFP construct, providing Wit-GFP flies prior to publication, and sharing project and manuscript advice; Mihaela Serpe for initial characterization of Punt-GFP flies; Melissa Ritter for cloning and analysis of Punt and Wit function; and Autumn Pace for preliminary studies of AP-1 components in the wing. We thank Myung-Jun Kim, Amanda Neisch, and Heidi Bretscher for helpful manuscript feedback.

Publisher Copyright:
Copyright: © 2022 Peterson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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