Manganese Redistribution by Calcium-stimulated Vesicle Trafficking Bypasses the Need for P-type ATPase Function |
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| Authors: | Néstor García-Rodríguez Javier Manzano-López Miguel Mu?oz-Bravo Elisabet Fernández-García Manuel Mu?iz Ralf Erik Wellinger |
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| Affiliation: | From the ‡Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla, 41092, Sevilla, Spain and ;the §Departamento de Biolgía Celular–Instituto de Biomedicina de Sevilla (IBiS), Universidad de Sevilla, 41012 Sevilla, Spain |
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| Abstract: | Regulation of intracellular ion homeostasis is essential for eukaryotic cell physiology. An example is provided by loss of ATP2C1 function, which leads to skin ulceration, improper keratinocyte adhesion, and cancer formation in Hailey-Hailey patients. The yeast ATP2C1 orthologue PMR1 codes for a Mn2+/Ca2+ transporter that is crucial for cis-Golgi manganese supply. Here, we present evidence that calcium overcomes the lack of Pmr1 through vesicle trafficking-stimulated manganese delivery and requires the endoplasmic reticulum Mn2+ transporter Spf1 and the late endosome/trans-Golgi Nramp metal transporter Smf2. Smf2 co-localizes with the putative Mn2+ transporter Atx2, and ATX2 overexpression counteracts the beneficial impact of calcium treatment. Our findings suggest that vesicle trafficking promotes organelle-specific ion interchange and cytoplasmic metal detoxification independent of calcineurin signaling or metal transporter re-localization. Our study identifies an alternative mode for cis-Golgi manganese supply in yeast and provides new perspectives for Hailey-Hailey disease treatment. |
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| Keywords: | Genetic Disease Golgi Manganese Vesicles Yeast PMR1 |
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