Slc30a10, a metal exporter, is a crucial manganese (Mn) efflux transporter. It plays a vital role in maintaining Mn homeostasis, with its function being essential for Mn excretion from hepatocytes and enterocytes [1,2,4]. Mutations in SLC30A10 can lead to Mn-induced neurotoxicity and other disorders, highlighting its importance in preventing Mn-related pathologies [1,2,4]. Genetic models, such as gene-knockout (KO) mice, have been instrumental in studying its function.

Whole-body Slc30a10-deficient mice develop severe Mn excess and impaired systemic and biliary Mn excretion [1]. Mice with liver-specific Slc30a10 deficiency have minimal Mn excess despite impaired biliary Mn excretion, and those with small-intestine-specific deficiency also have minimal Mn excess despite impaired Mn export into the small-intestine lumen [1]. Mice with combined liver and small-intestine Slc30a10 deficiency have less severe Mn excess than whole-body KO mice, suggesting other sites of Slc30a10 expression contribute to Mn homeostasis [1]. Pan-neuronal/glial Slc30a10 knockout mice show elevated Mn levels in specific brain regions during early postnatal development and neuromotor deficits in adolescence and adulthood [3].

In conclusion, Slc30a10 is essential for physiological Mn excretion and maintaining Mn homeostasis in the body. KO mouse models have revealed its role in preventing Mn-induced diseases, including neurological deficits, liver cirrhosis, and polycythemia. Understanding Slc30a10 function provides insights into Mn-related pathologies and potential therapeutic targets for treating Mn toxicity [1,3,5].

References:

1. Mercadante, Courtney J, Prajapati, Milankumar, Conboy, Heather L, Rao, Deepa B, Bartnikas, Thomas B. . Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. In The Journal of clinical investigation, 129, 5442-5461. doi:10.1172/JCI129710. https://pubmed.ncbi.nlm.nih.gov/31527311/

2. Chen, Pan, Bowman, Aaron B, Mukhopadhyay, Somshuvra, Aschner, Michael. 2015. SLC30A10: A novel manganese transporter. In Worm, 4, e1042648. doi:10.1080/21624054.2015.1042648. https://pubmed.ncbi.nlm.nih.gov/26430566/

3. Taylor, Cherish A, Grant, Stephanie M, Jursa, Thomas, Gonzales, Rueben A, Mukhopadhyay, Somshuvra. . SLC30A10 manganese transporter in the brain protects against deficits in motor function and dopaminergic neurotransmission under physiological conditions. In Metallomics : integrated biometal science, 15, . doi:10.1093/mtomcs/mfad021. https://pubmed.ncbi.nlm.nih.gov/36990693/

4. Mukhopadhyay, Somshuvra. 2017. Familial manganese-induced neurotoxicity due to mutations in SLC30A10 or SLC39A14. In Neurotoxicology, 64, 278-283. doi:10.1016/j.neuro.2017.07.030. https://pubmed.ncbi.nlm.nih.gov/28789954/

5. Prajapati, Milankumar, Zhang, Jared Z, Chiu, Lauren, Aghajan, Mariam, Bartnikas, Thomas B. 2024. Hepatic HIF2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency. In JCI insight, 9, . doi:10.1172/jci.insight.169738. https://pubmed.ncbi.nlm.nih.gov/38652538/