Study unveils novel protein that regulates iron build-up in chiton teeth

“Mineralization” or the structured deposition of biominerals in living organisms is a crucial process in the formation of hard surfaces ranging from shells, skeletons, and armors in invertebrates to mammalian teeth and bones. While silica and calcium are common organic minerals formed in various living organisms, few synthesize magnetite, an iron-based biomineral with strong magnetic properties.

Chitons are marine mollusks that inhabit rocky crevices and use their radula, a tongue-like feeding organ, to scrape off and feed on algae. They deposit magnetite onto their radular teeth, making them tough and wear-resistant, allowing them to grind rock surfaces efficiently. Interestingly, they replace lost teeth through the continuous formation of new teeth within the radular sac. While the mineral assembly and tooth maturation process within the radular sac is tightly regulated, the underlying mechanisms remain elusive.

To bridge this gap, researchers from Okayama University, Japan, sought to explore the molecular mechanisms and proteins that drive magnetite deposition in chiton teeth. The team, comprising Associate Professor Michiko Nemoto, Koki Okada (Ph.D. student), Professor Akira Satoh, Professor Hisao Moriya, and Associate Professor Kiori Obuse, have recently published their research findings in Vol 389, Issue 6760 of Science on August 07, 2025.

The researchers previously compared the protein expression profiles of tissues isolated from the radular base and the mineralized cusps of the gumboot chiton, Cryptochiton stelleri, and identified 22 proteins specific to the mineralized region. Following this lead, they found that radular teeth matrix protein 1 (RTMP1) and its homologs were chiton-specific and present in three other chiton species—Acanthopleura japonica, Acanthochitona achates, and Placiphorella stimpsoni.

Explaining the rationale behind their work, Dr. Nemoto says, “Owing to its magnetic characteristics, magnetite has been widely applied in hard disk drives, MRI contrast agents, and various biotechnology products used for cell separation and DNA extraction. Current methods of magnetite synthesis typically require high temperatures or hazardous chemicals. However, the protein we discovered, RTMP1, may enable a safer and more environmentally friendly approach to synthesis.”

The researchers examined the expression of RTMP1 across different stages of tooth formation and maturation. Stage 1 comprised transparent teeth primarily composed of chitin, stage 2 featured reddish-brown teeth due to ferrihydrite deposition, and stage 3 involved blackening of the teeth as ferrihydrite was converted to magnetite. They found that the RTMP1 homolog was highly expressed in cells isolated from stage 2, suggesting that RTMP1 was expressed during iron oxide deposition.

Next, localization studies revealed that RTMP1 homologs were uniformly expressed in the epithelial cells around the leading and trailing edges of immature teeth before iron deposition. They were also found to be pre-localized in the interior regions where iron deposition would occur. Subsequently, iron ions were transported by ferritin to the cusp, leading to deposition of iron oxide at the sites where RTMP1 homologs had been localized. As iron was deposited and the teeth matured, RTMP1 homologs became localized in the epithelial cells around the trailing edge of the teeth. Notably, the timing and localization pattern of RTMP1 homologs differed across different chiton species, likely due to their distinct tooth structures.

Further experiments revealed that RTMP1 homologs catalyzed the nucleation of iron oxide, guiding and enhancing the formation of iron oxide on chitin fibers. Finally, suppression of the RTMP1 homolog in A.japonica using RNA interference led to approximately 69% lower expression levels. Furthermore, this reduction correlated with decreased progression of mineralization (reduced coloration) during tooth maturation compared to controls.

Overall, these findings suggest that RTMP1 helps concentrate iron ions on the chitin fibers  and regulates iron oxide deposition within chiton teeth, making them ultrahard and durable. While iron is an essential element for organisms, including humans, it can be toxic at higher concentrations and contribute to diseases like cancer and neurodegenerative disorders. For decades, the mechanisms that drive iron deposition and its conversion to magnetite in chiton teeth have intrigued researchers. For the first time, this study reports a eukaryotic protein that regulates magnetite formation, opening doors for its use in various applications.

“RTMP1 holds potential for novel technologies requiring the controlled patterning of metal oxides at specific sites, which could be applied to the fabrication of sensors and memory devices. Additionally, because RTMP1 can regulate iron deposition, it may also aid research on iron-related diseases and cellular iron metabolism,” Dr. Nemoto concludes.

About Okayama University, Japan

As one of the leading universities in Japan, Okayama University aims to create and establish a new paradigm for the sustainable development of the world. Okayama University offers a wide range of academic fields, which become the basis of the integrated graduate schools. This not only allows us to conduct the most advanced and up-to-date research, but also provides an enriching educational experience.

Website: https://www.okayama-u.ac.jp/index_e.html

About Associate Professor Michiko Nemoto from Okayama University, Japan

Dr. Michiko Nemoto is an Associate Professor, Faculty of Environmental, Life, and Natural Sciences, Okayama University, and a  Visiting Researcher at the  National Hospital Organization Nagoya Medical Center. Her research focuses on elucidating the mechanisms underlying biomineralization of magnetite in chitons and silica in diatoms that can be applied in nanobiotechnological processes. She has authored over 35 publications across these research domains in various peer-reviewed journals.