TY - JOUR
T1 - Lysosome-Related Organelles Orchestrate Guanine Crystal Formation in Pigment Cells
AU - Gorelick-Ashkenazi, Anna
AU - Barzilay, Yuval
AU - Lerer-Goldshtein, Tali
AU - Olender, Tsviya
AU - Eyal, Zohar
AU - Glaser, May
AU - Broder, Yonatan
AU - Mishol, Nadav
AU - Deis, Rachael
AU - Kedmi, Merav
AU - Gur, Dvir
PY - 2026/1/6
Y1 - 2026/1/6
N2 - 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 previously unrecognized 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, acid-base regulation, and crystallization, with implications for LRO evolution and human disease.Competing Interest StatementThe authors have declared no competing interest.European Research Council- Starting Grant, 101077470Israel Science Foundation, https://ror.org/04sazxf24, 691/22
AB - 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 previously unrecognized 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, acid-base regulation, and crystallization, with implications for LRO evolution and human disease.Competing Interest StatementThe authors have declared no competing interest.European Research Council- Starting Grant, 101077470Israel Science Foundation, https://ror.org/04sazxf24, 691/22
U2 - 10.64898/2026.01.05.697611
DO - 10.64898/2026.01.05.697611
M3 - Article
SN - 2692-8205
JO - BioRxiv
JF - BioRxiv
ER -