GPI-anchored FGF directs cytoneme-mediated bidirectional contacts to regulate its tissue-specific dispersion.
GPI-anchored FGF directs cytoneme-mediated bidirectional contacts to regulate its tissue-specific dispersion.
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DOI：
10.1038/s41467-022-30417-1
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发表时间：
2022-06-16
影响因子：
16.6
通讯作者：
Roy, Sougata
中科院分区：
文献类型：
--
作者：
Du, Lijuan;Sohr, Alex;Li, Yujia;Roy, Sougata
信号蛋白如何产生大量信息来组织组织模式是理解形态发生的关键。在果蝇中，翅盘细胞中产生的FGF调节着与翅盘相关的气囊原基（ASP）的发育。在这里，我们发现FGF是糖基磷脂酰肌醇锚定在产生细胞表面的，这种修饰既抑制游离FGF的分泌，又促进靶特异性细胞素接触和接触依赖性FGF释放。FGF源细胞和ASP细胞扩展细胞素，这些细胞素在其表面呈现FGF和FGFR，并通过细胞粘附分子（CAM）样FGF-FGFR结合的接触远距离相互识别。接触介导的FGF-FGFR相互作用在ASP和源细胞中诱导双向反应，进而使fgf发送和fgf接收细胞素相互极化，以加强信号传导接触。随后，fgfr结合的FGF从源膜上解离细胞素接触，并将FGF特异性地传递给ASP细胞素，以实现旁分泌功能。因此，gpi锚定的FGF组织源细胞和受体细胞，并自我调节其细胞素介导的组织特异性分散。细胞素是一种信号丝状足，介导像fgf这样的特定靶标的远距离信号交流。Du等人的研究表明，果蝇的FGF固定在产生FGF的细胞表面，抑制游离FGF的分泌，激活接触依赖的FGF- fgfr双向相互作用，控制目标特异性细胞素接触和接触依赖的FGF释放。
How signaling proteins generate a multitude of information to organize tissue patterns is critical to understanding morphogenesis. In Drosophila, FGF produced in wing-disc cells regulates the development of the disc-associated air-sac-primordium (ASP). Here, we show that FGF is Glycosylphosphatidylinositol-anchored to the producing cell surface and that this modification both inhibits free FGF secretion and promotes target-specific cytoneme contacts and contact-dependent FGF release. FGF-source and ASP cells extend cytonemes that present FGF and FGFR on their surfaces and reciprocally recognize each other over distance by contacting through cell-adhesion-molecule (CAM)-like FGF-FGFR binding. Contact-mediated FGF-FGFR interactions induce bidirectional responses in ASP and source cells that, in turn, polarize FGF-sending and FGF-receiving cytonemes toward each other to reinforce signaling contacts. Subsequent un-anchoring of FGFR-bound-FGF from the source membrane dissociates cytoneme contacts and delivers FGF target-specifically to ASP cytonemes for paracrine functions. Thus, GPI-anchored FGF organizes both source and recipient cells and self-regulates its cytoneme-mediated tissue-specific dispersion. Cytonemes are signaling filopodia that mediate target-specific long-distance communications of signals like FGFs. Du et al. show that a Drosophila FGF is anchored to the FGF-producing cell surface, inhibiting free FGF secretion and activating contact-dependent bidirectional FGF-FGFR interactions, controlling target-specific cytoneme contacts and contact-dependent FGF release.
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