Identification of protein precursor for thyroid hormone synthesis in basal chordate ascidian Styela clava

Jin ZhangOcean University of China

Likun YangQingdao National Laboratory for Marine Science and Technology

Brice BeinsteinerHelmholtz Zentrum München

Yun MaOcean University of China

Jiankai WeiQingdao National Laboratory for Marine Science and Technology

Haiyan YuOcean University of China

Vincent LaudetOkinawa Institute of Science and Technology Graduate University

Bo DongQingdao National Laboratory for Marine Science and Technology

Nature Communications·February 7, 2026

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Abstract

Thyroid hormones (THs) are essential for development, growth, and metabolism in animals. Although TH synthesis is well described in vertebrates, it remains elusive in invertebrates due to the lack of identified thyroglobulin (TG) orthologs, the protein precursor for TH synthesis. Here, we identified a functional TG-like protein in ascidian Styela clava via immunoprecipitation-mass spectrometry combined with phylogenetic and expression analyses. In vitro iodination demonstrated that ScTG-like provides hormonogenic sites for TH synthesis. In vivo ScTg-like knockdown significantly reduced THs and inhibited larval metamorphosis. An invaginated follicle-like structure in the larval trunk, deposited with ScTG-like, was identified as the location for THs synthesis and storage. Furthermore, structural analysis of ScTG-like and predicted TG-like proteins across bilaterian phyla suggests that endogenous TH synthesis may be an ancestral and synapomorphic bilaterian trait. This study reports the identification of a TH precursor outside vertebrates, shedding lights on the evolution of the TH synthesis.

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