pH variations enable guanine crystal formation within iridosomes
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.
Authors
- Lothar Houben (ORCID: https://orcid.org/0000-0003-0200-3611)
- Ron Rotkopf (ORCID: https://orcid.org/0000-0001-9503-7348)
- Anna Gorelick-Ashkenazi
- Andrea Sorrentino (ORCID: https://orcid.org/0000-0002-3235-8950)
- Neta Varsano (ORCID: https://orcid.org/0000-0002-7443-7315)
- Ifat Kaplan‐Ashiri (ORCID: https://orcid.org/0000-0003-4058-3477)
- Dvir Gur (ORCID: https://orcid.org/0000-0002-9140-1621)
- Rebecca A. Metzler (ORCID: https://orcid.org/0000-0001-9196-9084)
- Katya Rechav (ORCID: https://orcid.org/0000-0003-4664-5704)
- Leeor Kronik (ORCID: https://orcid.org/0000-0001-6791-8658)
- Rachael Deis (ORCID: https://orcid.org/0000-0002-3073-1395)
- Zohar Eyal (ORCID: https://orcid.org/0000-0002-8966-0624)
- Michal Hartstein
- Peter Rez
- Yuval Barzilay (ORCID: https://orcid.org/0000-0002-2489-8834)
- Yonatan Broder (ORCID: https://orcid.org/0009-0000-1596-0176)
- Asher Perry Kellum
Institutions
- ALBA Synchrotron (Spain) (ES)
- Colgate University (US)
- Weizmann Institute of Science (IL)
- Arizona State University (US)
Publication Details
- Journal
- Nature Chemical Biology
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1038/s41589-025-02020-0
- Citations
- 1
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 0.91
Funders
- European Commission
- Weizmann Institute of Science