ArticlePloS one2013
SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a model of lactation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Circ72688 Drives Breast Cancer Invasion and Metastasis via the miR-654-5p/ORAI2 Axis.Oncology research · 2026Article
- Defining the interactome of the pancreas-specific SPCA2 isoform (SPCA2C) identifies unique links to store-operated CaThe FEBS journal · 2025Article
- Differential functional role of Orai1 variants in constitutive CaThe Journal of biological chemistry · 2024Article
- The ins and outs of mammary gland calcium and zinc transport: A brief review.JDS communications · 2023Review
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- Quantification of FAM20A in human milk and identification of calcium metabolism proteins.Physiological reports · 2021Article
- Review
- CaCancers · 2021Review
- The Orai1-AC8 Interplay: How Breast Cancer Cells Escape from Orai1 Channel Inactivation.Cells · 2021Review
- CaCancers · 2021Review
- More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.International journal of molecular sciences · 2021Review
- The N and C-termini of SPCA2 regulate differently Kv10.1 function: role in the collagen 1-induced breast cancer cell survival.American journal of cancer research · 2021Article
- Molecular Choreography and Structure of CaMembranes · 2020Review
- Calcium Metabolism and Breast Cancer: Echoes of Lactation?Current opinion in endocrine and metabolic research · 2020Article
- Kv10.1 Regulates Microtubule Dynamics during Mitosis.Cancers · 2020Article
- Primary Active CaCold Spring Harbor perspectives in biology · 2020Review
- Pathological role of ion channels and transporters in the development and progression of triple-negative breast cancer.Cancer cell international · 2020Review
- Subtype specific targeting of calcium signaling in breast cancer.Cell calcium · 2020Article
- A CaMolecular cancer research : MCR · 2019Article
- An N-terminal CaThe Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
An unconventional interaction between SPCA2, an isoform of the Golgi secretory pathway Ca(2+)-ATPase, and the Ca(2+) influx channel Orai1, has previously been shown to contribute to elevated Ca(2+) influx in breast cancer derived cells. In order to investigate the physiological role of this interaction, we examined expression and localization of SPCA2 and Orai1 in mouse lactating mammary glands. We observed co-induction and co-immunoprecipitation of both proteins, and isoform-specific differences in the localization of SPCA1 and SPCA2. Three-dimensional cultures of normal mouse mammary epithelial cells were established using lactogenic hormones and basement membrane. The mammospheres displayed elevated Ca(2+) influx by store independent mechanisms, consistent with upregulation of both SPCA2 and Orai1. Knockdown of either SPCA2 or Orai1 severely depleted Ca(2+) influx and interfered with mammosphere differentiation. We show that SPCA2 is required for plasma membrane trafficking of Orai1 in mouse mammary epithelial cells and that this function can be replaced, at least in part, by a membrane-anchored C-terminal domain of SPCA2. These findings clearly show that SPCA2 and Orai1 function together to regulate Store-independent Ca(2+) entry (SICE), which mediates the massive basolateral Ca(2+) influx into mammary epithelia to support the large calcium transport requirements for milk secretion.
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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.