PUBLICATION
Lysosome-related organelles orchestrate guanine crystal formation in pigment cells
- Authors
- Gorelick-Ashkenazi, A., Barzilay, Y., Lerer-Goldshtein, T., Olender, T., Eyal, Z., Glaser, M., Broder, Y., Mishol, N., Deis, R., Kedmi, M., Gur, D.
- ID
- ZDB-PUB-260409-5
- Date
- 2026
- Source
- Proceedings of the National Academy of Sciences of the United States of America 123: e2524305123 (Journal)
- Registered Authors
- Eyal, Zohar, Gur, Dvir, Lerer-Goldshtein, Tali
- Keywords
- crystals, guanine, iridosome, lysosome related organelle, zebrafish
- MeSH Terms
- none
- PubMed
- 41950095 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Gorelick-Ashkenazi, A., Barzilay, Y., Lerer-Goldshtein, T., Olender, T., Eyal, Z., Glaser, M., Broder, Y., Mishol, N., Deis, R., Kedmi, M., Gur, D. (2026) Lysosome-related organelles orchestrate guanine crystal formation in pigment cells. Proceedings of the National Academy of Sciences of the United States of America. 123:e2524305123.
Abstract
Iridosomes, the guanine crystal-forming organelles of pigment-producing iridophores, are among the most versatile, visually striking yet mechanistically uncharacterized organelles in vertebrate biology. Lysosome-related organelles (LROs) support cell type-specific functions by adapting endolysosomal pathways for specialized roles. Here, we show that iridosomes represent a subtype of LROs. Using transcriptomic profiling of zebrafish iridophores, CRISPR-Cas9-mediated gene disruption, and cryogenic transmission electron microscopy, we define the molecular program underlying iridosome biogenesis. Iridosomes have evolved unique adaptations for crystal growth while retaining core features of other LROs. Key regulators, including Rab32a, Ap3m2, and Hps5, are essential for crystal formation, with gene knockouts causing reduced crystal number, altered morphology, and distinct maturation defects. We further identify hallmark LRO features in iridosomes, including intraluminal vesicles and pH-regulated developmental transitions. Cross-species transcriptomic analysis confirms that iridosomes share an LRO signature across vertebrates, including teleost fish and reptiles, suggesting ancient evolutionary origins. These findings establish iridosomes as crystalline LROs and as a model for investigating how cells construct structurally specialized organelles through coordinated trafficking and crystallization, with implications for LRO evolution and human disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping