The Drosophila Hedgehog receptor component Interference hedgehog (Ihog) mediates cell–cell interactions through trans-homophilic binding

Wu, Xuefeng; Zhang, Ya; Chuang, Kun-Han; Cai, Xiaona; Ajaz, Humna; Zheng, Xiaoyan

doi:10.1074/jbc.ra119.008744

Cited by 10 publications

(34 citation statements)

References 38 publications

(43 reference statements)

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“…In agreement, we have observed that the ectopic expression of a variant of Ihog lacking Fn1 does not accumulate Hh in the P compartment as the wild type Ihog does. The Ihog amino-acids mediating the interaction with Hh have been also identified on the Fn1 extracellular domain in tissue culture cells (Wu et al ., 2019). The amino-acids described (Wu et al ., 2019) are not the same as the ones identified here, although they are in the same protein region.…”

Section: Discussionmentioning

confidence: 99%

“…The Ihog amino-acids mediating the interaction with Hh have been also identified on the Fn1 extracellular domain in tissue culture cells (Wu et al ., 2019). The amino-acids described (Wu et al ., 2019) are not the same as the ones identified here, although they are in the same protein region. Alteration of the amino-acids D558N, N559S, E561Q in the Fn1 domain (Ihog Fn1***) impedes Hh build-up.…”

Section: Discussionmentioning

confidence: 99%

“…Hh have been also identified on the Fn1 extracellular domain in tissue culture cells (Wu et al, 2019). The amino-acids described (Wu et al, 2019) et al, 2006). However, the expression of a construct only carrying the wild type Fn1 reveals that Fn1 alone recruits very low Hh levels.…”

Section: Ihog Interactions With Glypicans Hh and Ptcmentioning

confidence: 98%

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Glypicans specifically regulate Hedgehog signaling through their interaction with Ihog in cytonemes

Simon

Jiménez-Jiménez

Seijo-Barandiarán

et al. 2020

Preprint

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The conserved family of Hedgehog (Hh) signaling proteins plays a key role in cell-cell communication in development, tissue repair and cancer progression. These proteins can act as morphogens, inducing responses dependent on the ligand concentration in target cells located at a distance. Hh proteins are lipid modified and thereby have high affinity for membranes, which hinders the understanding of their spreading across tissues. Direct contact between cell membranes by filopodia-like structures (also known as cytonemes) could be the simplest explanation for Hh dispersal. To better understand this signaling mechanism, we have analyzed in Drosophila the interaction between the glypicans that, besides for other pathways, are necessary for Hh signaling, plus the adhesion molecules and Hh coreceptors Ihog and Boi. We describe that glypicans (Dally and Dally-like protein) are required to maintain Ihog, but not Boi, protein levels. We also show that ectopic Ihog stabilizes cytonemes through its interaction with glypicans, and we determine that two Ihog fibronectin III domains are essential for this interaction. Our data suggest that this interaction with Ihog in cytonemes confers the specificity of glypicans for Hh signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Glypicans specifically regulate Hedgehog signaling through their interaction with Ihog in cytonemes

Simon

Jiménez-Jiménez

Seijo-Barandiarán

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Previously, we showed that the Ihog Fn1 domain not only plays an essential role in Hh signal transduction but also mediates cell-cell interactions in a homophilic manner (Hsia et al 2017; Wu et al 2019). Because our data indicated that Ihog stabilized cytonemes through the Fn1 domain in a manner independent of Hh receptor function (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1, 2), we hypothesized that Ihog Fn1-mediated homophilic trans interactions were responsible for cytoneme stabilization. The region that we identified as mediating the trans Ihog-Ihog interaction overlaps with the region that mediates the interaction with Hh on the Ihog Fn1 domain and includes a region where the negatively charged glycan heparin binds (McLellan et al 2006; Wu et al 2019). In vitro , heparin is required for not only Ihog-Hh binding but also Ihog-Ihog homophilic trans interactions (McLellan et al 2006; Wu et al 2019).…”

Section: Resultsmentioning

confidence: 99%

Competitive coordination of the dual roles of the Hedgehog co-receptor in homophilic adhesion and signal reception

Yang

Zhang

Yang

et al. 2021

Preprint

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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 independently from its role in the Hh receptor. By combining experimental data and mathematical modeling, we determined that the Hh-Ihog heterophilic interaction dominates and that Hh can disrupt and displace Ihog molecules involved in trans-homophilic binding. Our results support a model in which the two functions— homophilic adhesion and ligand binding— cooperate to enable Hh transport and signaling along cytonemes.

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Ihog proteins contribute to integrin-mediated focal adhesions

Liu

Zhang

et al. 2022

Sci. China Life Sci.

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The Drosophila Hedgehog receptor component Interference hedgehog (Ihog) mediates cell–cell interactions through trans-homophilic binding

Cited by 10 publications

References 38 publications

Glypicans specifically regulate Hedgehog signaling through their interaction with Ihog in cytonemes

Glypicans specifically regulate Hedgehog signaling through their interaction with Ihog in cytonemes

Competitive coordination of the dual roles of the Hedgehog co-receptor in homophilic adhesion and signal reception

Ihog proteins contribute to integrin-mediated focal adhesions

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