Reference - Detail
| RRC ID | 70791 |
|---|---|
| Author | Yang S, Zhang Y, Yang C, Wu X, El Oud SM, Chen R, Cai X, Wu XS, Lan G, Zheng X. |
| Title | Competitive coordination of the dual roles of the Hedgehog co-receptor in homophilic adhesion and signal reception. |
| Journal | Elife |
| Abstract |
Hedgehog (Hh) signaling patterns embryonic tissues and contributes to homeostasis in adults. In Drosophila, Hh transport and signaling are thought to occur along a specialized class of actin-rich filopodia, termed cytonemes. Here, we report that Interference hedgehog (Ihog) not only forms a Hh receptor complex with Patched to mediate intracellular signaling, but Ihog also engages in trans-homophilic binding leading to cytoneme stabilization in a manner independent of its role as the Hh receptor. Both functions of Ihog (trans-homophilic binding for cytoneme stabilization and Hh binding for ligand sensing) involve a heparin-binding site on the first fibronectin repeat of the extracellular domain. Thus, the Ihog-Ihog interaction and the Hh-Ihog interaction cannot occur simultaneously for a single Ihog molecule. By combining experimental data and mathematical modeling, we determined that Hh-Ihog heterophilic interaction dominates and Hh can disrupt and displace Ihog molecules involved in trans-homophilic binding. Consequently, we proposed that the weaker Ihog-Ihog trans interaction promotes and stabilizes direct membrane contacts along cytonemes and that, as the cytoneme encounters secreted Hh ligands, the ligands trigger release of Ihog from trans Ihog-Ihog complex enabling transport or internalization of the Hh ligand-Ihog-Patched -receptor complex. Thus, the seemingly incompatible functions of Ihog in homophilic adhesion and ligand binding cooperate to assist Hh transport and reception along the cytonemes. |
| Volume | 10 |
| Published | 2021-5-18 |
| DOI | 10.7554/eLife.65770 |
| PII | 65770 |
| PMID | 34003115 |
| PMC | PMC8131103 |
| MeSH | Animals Cell Line Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Hedgehog Proteins / genetics Hedgehog Proteins / metabolism* Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Models, Theoretical Protein Domains Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism* Signal Transduction / physiology* |
| IF | 7.08 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | DGRC#115064 |