ArticleProceedings of the National Academy of Sciences of the United States of America2011
Identification of a gain-of-function mutation in a Golgi P-type ATPase that enhances Mn2+ efflux and protects against toxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 82 citations in OpenAlex.
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Synchrotron XRF Imaging Reveals Manganese Accumulation in the Golgi and Post-Synapses of Neurons and Enhanced Uptake in Astrocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neuron-specific modulation of SLC30A10 identifies dopaminergic and glutamatergic neurons as targets of manganese-induced motor disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular mechanisms of SLC30A10-mediated manganese transport.Nature communications · 2025Article
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Case of Congenital Hemolytic Anemia withChildren (Basel, Switzerland) · 2023Article
- Insights into the regulation of cellular MnBiochimica et biophysica acta. Molecular basis of disease · 2023Article
- Cryo-EM structures of human SPCA1a reveal the mechanism of CaScience advances · 2023Article
- A genetically encoded fluorescent sensor for manganese(II), engineered from lanmodulin.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Review
- Up-regulation of the manganese transporter SLC30A10 by hypoxia-inducible factors defines a homeostatic response to manganese toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Assessment of Concentrations of Heavy Metals in Postmyocardial Infarction Patients and Patients Free from Cardiovascular Event.Cardiology research and practice · 2021Article
- The impact of manganese on neurotransmitter systems.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2020Review
- Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy.Toxins · 2020Review
- Brain manganese and the balance between essential roles and neurotoxicity.The Journal of biological chemistry · 2020Review
- ZIP14 is degraded in response to manganese exposure.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Characterization of Hailey-Hailey Disease-mutants in presence and absence of wild type SPCA1 using Saccharomyces cerevisiae as model organism.Scientific reports · 2019Article
- A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus.Nucleic acids research · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
P-type ATPases transport a wide array of ions, regulate diverse cellular processes, and are implicated in a number of human diseases. However, mechanisms that increase ion transport by these ubiquitous proteins are not known. SPCA1 is a P-type pump that transports Mn(2+) from the cytosol into the Golgi. We developed an intra-Golgi Mn(2+) sensor and used it to screen for mutations introduced in SPCA1, on the basis of its predicted structure, which could increase its Mn(2+) pumping activity. Remarkably, a point mutation (Q747A) predicted to increase the size of its ion permeation cavity enhanced the sensor response and a compensatory mutation restoring the cavity to its original size abolished this effect. In vivo and in vitro Mn(2+) transport assays confirmed the hyperactivity of SPCA1-Q747A. Furthermore, increasing Golgi Mn(2+) transport by expression of SPCA1-Q747A increased cell viability upon Mn(2+) exposure, supporting the therapeutic potential of increased Mn(2+) uptake by the Golgi in the management of Mn(2+)-induced neurotoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.