pH variations enable guanine crystal formation within iridosomes

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology Pub Date : 2025-09-02 DOI:10.1038/s41589-025-02020-0

Zohar Eyal, Rachael Deis, Anna Gorelick-Ashkenazi, Yuval Barzilay, Yonatan Broder, Asher Perry Kellum, Neta Varsano, Michal Hartstein, Andrea Sorrentino, Ron Rotkopf, Ifat Kaplan-Ashiri, Katya Rechav, Rebecca Metzler, Lothar Houben, Leeor Kronik, Peter Rez, Dvir Gur

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Abstract

Many animals produce vivid colors by reflecting and amplifying light with stacked guanine crystals within membrane-bound organelles called iridosomes. While the presence of guanine crystals in iridosomes is well documented, the mechanisms facilitating the accumulation of water-insoluble guanine and driving its crystallization remain unclear. Here we used cryo-electron microscopy, live-cell pH imaging, pharmacological perturbations and spectroscopy to study iridosome maturation in zebrafish. Cryo-electron and synchrotron-based soft X-ray microscopies revealed that amorphous guanine initially accumulates in early-stage iridosomes in its protonated state. Live-cell imaging with a pH sensor demonstrated that early iridosomes are acidic, with pH gradually neutralizing during development. Inhibiting V-ATPase disrupted this acidification and significantly reduced crystal formation, indicating its role in pH regulation. Our findings reveal insights into the molecular mechanisms facilitating guanine formation within iridosomes, emphasizing the pivotal role of pH alternations in the precise formation of biogenic crystals.

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pH值的变化使鸟嘌呤晶体在虹膜小体内形成

许多动物通过在被称为虹膜小体的膜结合细胞器中堆叠鸟嘌呤晶体来反射和放大光线，从而产生鲜艳的颜色。虽然虹彩小体中鸟嘌呤晶体的存在已被充分记录，但促进不溶于水的鸟嘌呤积累和驱动其结晶的机制仍不清楚。在这里，我们使用冷冻电子显微镜，活细胞pH成像，药理学摄动和光谱学来研究斑马鱼虹膜体的成熟。低温电子和基于同步加速器的软x射线显微镜显示，无定形鸟嘌呤最初以质子化状态积聚在早期虹膜小体中。使用pH传感器的活细胞成像显示，早期虹膜小体呈酸性，在发育过程中pH值逐渐中和。抑制V-ATPase破坏了这种酸化并显著减少了晶体形成，表明其在pH调节中的作用。我们的发现揭示了虹膜小体中促进鸟嘌呤形成的分子机制，强调了pH变化在生物源晶体精确形成中的关键作用。

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来源期刊

Nature chemical biology 生物-生化与分子生物学

CiteScore

23.90

自引率

1.40%

发文量

238

审稿时长

12 months

期刊介绍： Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.