Eyal Zohar, Deis Rachael, Gorelick-Ashkenazi Anna, Barzilay Yuval, Broder Yonatan, Kellum Asher Perry, Varsano Neta, Hartstein Michal, Sorrentino Andrea, Rotkopf Ron, Kaplan-Ashiri Ifat, Rechav Katya, Metzler Rebecca, Houben Lothar, Kronik Leeor, Rez Peter, Gur Dvir
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Nat Chem Biol. 2025 Sep 2. doi: 10.1038/s41589-025-02020-0.
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.
许多动物通过位于称为虹彩体的膜结合细胞器内的堆叠鸟嘌呤晶体反射和放大光线来产生鲜艳的颜色。虽然虹彩体中鸟嘌呤晶体的存在已有充分记录，但促进水不溶性鸟嘌呤积累并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、药理学扰动和光谱学来研究斑马鱼虹彩体的成熟过程。冷冻电子显微镜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累在早期虹彩体中。用pH传感器进行的活细胞成像表明，早期虹彩体呈酸性，在发育过程中pH值逐渐中和。抑制V-ATPase会破坏这种酸化并显著减少晶体形成，表明其在pH调节中的作用。我们的研究结果揭示了促进虹彩体内鸟嘌呤形成的分子机制，强调了pH值变化在生物晶体精确形成中的关键作用。
