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丝状伪足对于类固醇释放至关重要。

Filopodia are essential for steroid release.

作者信息

Simon Eléanor, Bonche Raphaël, Maarouf Yassine, Nawrot-Esposito Marie-Paule, Romero Nuria Magdalena

机构信息

Université Côte d'Azur, INRAE, CNRS, Sophia Agrobiotech Institute (ISA), Sophia Antipolis, France.

Université Côte d'Azur, INRAE, CNRS, INSERM, Sophia Agrobiotech Institute (ISA), Sophia Antipolis, France.

出版信息

Nat Commun. 2025 Jul 1;16(1):5501. doi: 10.1038/s41467-025-60579-7.

DOI:10.1038/s41467-025-60579-7
PMID:40593541
Abstract

Steroid hormones, crucial for development and physiology, were traditionally believed to diffuse passively through membranes. However, recent evidence shows insect steroid ecdysone being secreted via regulated exocytosis, but the mechanisms ensuring successful hormone release into circulation remain unclear. Our study identifies specialized membrane protrusions, signaling filopodia, in the Drosophila prothoracic gland as essential for vesicle-mediated steroid release. Confocal imaging reveals that these actin- and tubulin-rich structures form a membrane-intertwined basal domain critical for secretion. Disrupting filopodia by interfering with basement membrane interactions-Perlecan or β-integrin-or filopodia-specific protein expression-α-actinin-significantly reduces ecdysone signaling by impairing its release, despite proper production in the gland. Additionally, filopodia dynamics, such as length and density, align with secretion timing and hormone circulating levels, suggesting their role in synchronizing release with physiological needs. The systematic presence of membrane protrusions in steroid-secreting glands across species prompts a comprehensive re-evaluation of steroid release mechanisms.

摘要

类固醇激素对发育和生理过程至关重要,传统观点认为它们可被动扩散穿过细胞膜。然而,最近有证据表明昆虫类固醇蜕皮激素是通过调节性胞吐作用分泌的,但确保激素成功释放到循环系统中的机制仍不清楚。我们的研究确定了果蝇前胸腺中一种特殊的膜突出结构——信号丝状伪足,它对囊泡介导的类固醇释放至关重要。共聚焦成像显示,这些富含肌动蛋白和微管蛋白的结构形成了一个对分泌至关重要的膜交织基底结构域。通过干扰基底膜相互作用(如基底膜蛋白聚糖或β-整合素)或丝状伪足特异性蛋白表达(如α-辅肌动蛋白)来破坏丝状伪足,尽管腺体中激素产生正常,但会通过损害其释放而显著降低蜕皮激素信号。此外,丝状伪足的动态变化,如长度和密度,与分泌时间和激素循环水平一致,表明它们在使释放与生理需求同步方面发挥作用。跨物种类固醇分泌腺中膜突出结构的系统性存在促使人们对类固醇释放机制进行全面重新评估。

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本文引用的文献

1
The cellular protrusions for inter-cellular material transfer: similarities between filopodia, cytonemes, tunneling nanotubes, viruses, and extracellular vesicles.用于细胞间物质转移的细胞突起:丝状伪足、细胞触须、隧道纳米管、病毒和细胞外囊泡之间的相似性
Front Cell Dev Biol. 2024 Jul 5;12:1422227. doi: 10.3389/fcell.2024.1422227. eCollection 2024.
2
How micron-sized exocrine vesicles release content: A comparison with sub-micron endocrine vesicles.微米级外分泌小泡如何释放内容物:与亚微米级内分泌小泡的比较。
J Cell Biol. 2023 Nov 6;222(11). doi: 10.1083/jcb.202310047. Epub 2023 Oct 20.
3
Filopodia In Vitro and In Vivo.
丝状伪足的体外与体内研究
Annu Rev Cell Dev Biol. 2023 Oct 16;39:307-329. doi: 10.1146/annurev-cellbio-020223-025210. Epub 2023 Jul 5.
4
Requirement of Cholesterol for Calcium-Dependent Vesicle Fusion by Strengthening Synaptotagmin-1-Induced Membrane Bending.胆固醇通过增强突触融合蛋白 1 诱导的膜弯曲对钙依赖性囊泡融合的需求。
Adv Sci (Weinh). 2023 May;10(15):e2206823. doi: 10.1002/advs.202206823. Epub 2023 Apr 14.
5
Microscopic and biochemical monitoring of endosomal trafficking and extracellular vesicle secretion in an endogenous in vivo model.在一个内源性体内模型中对内体运输和细胞外囊泡分泌进行微观和生化监测。
J Extracell Vesicles. 2022 Sep;11(9):e12263. doi: 10.1002/jev2.12263.
6
Actin-microtubule dynamic composite forms responsive active matter with memory.肌动蛋白-微管动态复合形成具有记忆的响应性活性物质。
Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2209522119. doi: 10.1073/pnas.2209522119. Epub 2022 Jul 25.
7
Sex steroid hormones in urinary exosomes as biomarkers for the prediction of prostate cancer.尿外泌体中的性类固醇激素作为预测前列腺癌的生物标志物。
Clin Chim Acta. 2022 Jun 1;531:389-398. doi: 10.1016/j.cca.2022.04.995. Epub 2022 Apr 27.
8
Glypicans define unique roles for the Hedgehog co-receptors boi and ihog in cytoneme-mediated gradient formation.Glypicans 在 Hedgehog 共受体 boi 和 ihog 在纤毛介导的梯度形成中定义了独特的作用。
Elife. 2021 Aug 6;10:e64581. doi: 10.7554/eLife.64581.
9
Cytonemes with complex geometries and composition extend into invaginations of target cells.具有复杂几何形状和组成的丝状伪足延伸到靶细胞的内陷中。
J Cell Biol. 2021 May 3;220(5). doi: 10.1083/jcb.202101116.
10
How does curvature affect the free-energy barrier of stalk formation? Small vesicles vs apposing, planar membranes.曲率如何影响茎形成的自由能势垒?小泡与面对的、平面的膜。
Eur Biophys J. 2021 Mar;50(2):253-264. doi: 10.1007/s00249-020-01494-1. Epub 2021 Feb 6.