RRC ID |
70791
|
著者 |
Yang S, Zhang Y, Yang C, Wu X, El Oud SM, Chen R, Cai X, Wu XS, Lan G, Zheng X.
|
タイトル |
Competitive coordination of the dual roles of the Hedgehog co-receptor in homophilic adhesion and signal reception.
|
ジャーナル |
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.
|
巻・号 |
10
|
公開日 |
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
|
リソース情報 |
ショウジョウバエ |
DGRC#115064 |