ArticleProceedings of the National Academy of Sciences of the United States of America2015
Essential role of Orai1 store-operated calcium channels in lactation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 90 citations in OpenAlex.
- Insulin resistance is associated with mammary mitochondrial dysfunction at the onset of human lactation.The Journal of clinical investigation · 2026Article
- Little women: the relevance and reliance on mouse models for mammary gland research and next steps for translation.Journal of mammary gland biology and neoplasia · 2025Review
- A subset of Orai1α and Orai1β subunits heteromerizes to form CRAC channels.Cell communication and signaling : CCS · 2025Article
- Methods for Imaging Intracellular Calcium Signals in the Mouse Mammary Epithelium in Two and Three Dimensions.Methods in molecular biology (Clifton, N.J.) · 2025Article
- TP53I11 Functions Downstream of Multiple MicroRNAs to Increase ER Calcium Levels and Inhibits Cancer Cell Proliferation.International journal of molecular sciences · 2024Article
- Differential functional role of Orai1 variants in constitutive CaThe Journal of biological chemistry · 2024Article
- Article
- Postbiotics of Lacticaseibacillus paracasei CECT 9610 and Lactiplantibacillus plantarum CECT 9608 attenuates store-operated calcium entry and FAK phosphorylation in colorectal cancer cells.Molecular oncology · 2024Article
- Calcium signaling in oocyte quality and functionality and its application.Frontiers in endocrinology · 2024Review
- Gap junction-mediated contraction of myoepithelial cells induces the peristaltic transport of sweat in human eccrine glands.Communications biology · 2023Article
- Orai1α and Orai1β support calcium entry and mammosphere formation in breast cancer stem cells.Scientific reports · 2023Article
- The ins and outs of mammary gland calcium and zinc transport: A brief review.JDS communications · 2023Review
- Toll-like receptor 4 activation enhances Orai1-mediated calcium signal promoting cytokine production in spinal astrocytes.Cell calcium · 2022Article
- Calcium Signalling in Breast Cancer Associated Bone Pain.International journal of molecular sciences · 2022Review
- Role of the Phospholipase C Pathway and Calcium Mobilization in Oxytocin-Induced Contraction of Lacrimal Gland Myoepithelial Cells.Investigative ophthalmology & visual science · 2021Article
- The molecular basis of mammary gland development and epithelial differentiation.Seminars in cell & developmental biology · 2021Review
- Elevated serotonin coordinates mammary metabolism in dairy cows.Physiological reports · 2021Article
- Got Milk? Identifying and Characterizing Lactation Defects in Genetically-Engineered Mouse Models.Journal of mammary gland biology and neoplasia · 2020Review
- Calcium Metabolism and Breast Cancer: Echoes of Lactation?Current opinion in endocrine and metabolic research · 2020Article
- Multiscale imaging of basal cell dynamics in the functionally mature mammary gland.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The nourishment of neonates by nursing is the defining characteristic of mammals. However, despite considerable research into the neural control of lactation, an understanding of the signaling mechanisms underlying the production and expulsion of milk by mammary epithelial cells during lactation remains largely unknown. Here we demonstrate that a store-operated Ca(2+) channel subunit, Orai1, is required for both optimal Ca(2+) transport into milk and for milk ejection. Using a novel, 3D imaging strategy, we visualized live oxytocin-induced alveolar unit contractions in the mammary gland, and we demonstrated that in this model milk is ejected by way of pulsatile contractions of these alveolar units. In mammary glands of Orai1 knockout mice, these contractions are infrequent and poorly coordinated. We reveal that oxytocin also induces a large transient release of stored Ca(2+) in mammary myoepithelial cells followed by slow, irregular Ca(2+) oscillations. These oscillations, and not the initial Ca(2+) transient, are mediated exclusively by Orai1 and are absolutely required for milk ejection and pup survival, an observation that redefines the signaling processes responsible for milk ejection. These findings clearly demonstrate that Ca(2+) is not just a substrate for nutritional enrichment in mammals but is also a master regulator of the spatiotemporal signaling events underpinning mammary alveolar unit contraction. Orai1-dependent Ca(2+) oscillations may represent a conserved language in myoepithelial cells of other secretory epithelia, such as sweat glands, potentially shedding light on other Orai1 channelopathies, including anhidrosis (an inability to sweat).
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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.