Structural and functional plasticity of metal-responsive transcription factor 1 (MTF-1) within Lophotrochozoa

Control of metal ion metabolism in animals is crucial for their survival. In this context, the regulation of metallothioneins (MTs), key proteins in metal metabolism and detoxification, by the metal regulatory transcription factor MTF-1 is well established in vertebrates and Drosophila melanogaster. However, the metal-dependent regulation of MT genes in most other invertebrates remains poorly understood, with MTF-1 so far identified in only a few invertebrate species. In the present study, we identified the presence of MTF-1 in diverse species within Lophotrochozoa. Specifically, we confirmed the functionality of MTF-1 from Helix pomatia (Gastropoda) and Lumbricus terrestris (Annelida) through in vitro co-expression studies using a dual-luciferase assay. We also demonstrate that the conserved zinc finger region appears to be the functional centrepiece of MTF-1 throughout all animal phyla, supporting core transcription factor functions across different species. In contrast, there is high variability in the up- and downstream MTF-1 sequences which may reflect the potential for additional functions, such as species- and habitat-specific adaptations. Our study provides a comprehensive framework for better understanding MTF-1 sequence and functional variability between closely and more distantly related species.