ArticlePloS one2015
Calmodulin Interacts with the Sodium/Calcium Exchanger NCX1 to Regulate Activity.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Article
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- Environment-induced heat stress causes ventricular-dependent biochemical changes in the heart in female pigs.Physiological reports · 2025Article
- Naringin attenuates angiotensin II induced cardiac hypertrophy by inhibiting carbonic anhydrase II.Scientific reports · 2025Article
- An In Vivo Model of Estrogen Supplementation Concerning the Expression of CaJournal of cardiovascular development and disease · 2024Article
- Calcium and Non-Penetrating Traumatic Brain Injury: A Proposal for the Implementation of an Early Therapeutic Treatment for Initial Head Insults.Biomolecules · 2024Review
- The Complex Interplay between Toxic Hallmark Proteins, Calmodulin-Binding Proteins, Ion Channels, and Receptors Involved in Calcium Dyshomeostasis in Neurodegeneration.Biomolecules · 2024Review
- Antagonizing Sec62 function in intracellular CaFrontiers in physiology · 2022Article
- Renal calcium and magnesium handling in Gitelman syndrome.American journal of translational research · 2022Review
- Diffuse Axonal Injury: Clinical Prognostic Factors, Molecular Experimental Models and the Impact of the Trauma Related Oxidative Stress. An Extensive Review Concerning Milestones and Advances.International journal of molecular sciences · 2021Review
- A novel substrate for arrhythmias in Chagas disease.PLoS neglected tropical diseases · 2021Article
- Calmodulin regulates the olfactory performance in Drosophila melanogaster.Scientific reports · 2021Article
- Modulation of the cardiac NaCell calcium · 2020Review
- Dynamin and reverse-mode sodium calcium exchanger blockade confers neuroprotection from diffuse axonal injury.Cell death & disease · 2019Article
- Knockdown of sodium-calcium exchanger 1 induces epithelial-to-mesenchymal transition in kidney epithelial cells.The Journal of biological chemistry · 2017Article
- Calmodulin modulates the CaIBRO reports · 2017Article
- Calmodulin binds and modulates KThe Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in intracellular Ca2+ concentrations ([Ca2+]i) are an important signal for various physiological activities. The Na+/Ca2+ exchangers (NCX) at the plasma membrane transport Ca2+ into or out of the cell according to the electrochemical gradients of Na+ and Ca2+ to modulate [Ca2+]i homeostasis. Calmodulin (CaM) senses [Ca2+]i changes and relays Ca2+ signals by binding to target proteins such as channels and transporters. However, it is not clear how calmodulin modulates NCX activity. Using CaM as a bait, we pulled down the intracellular loops subcloned from the NCX1 splice variants NCX1.1 and NCX1.3. This interaction requires both Ca2+ and a putative CaM-binding segment (CaMS). To determine whether CaM modulates NCX activity, we co-expressed NCX1 splice variants with CaM or CaM1234 (a Ca2+-binding deficient mutant) in HEK293T cells and measured the increase in [Ca2+]i contributed by the influx of Ca2+ through NCX. Deleting the CaMS from NCX1.1 and NCX1.3 attenuated exchange activity and decreased membrane localization. Without the mutually exclusive exon, the exchange activity was decreased and could be partially rescued by CaM1234. Point-mutations at any of the 4 conserved a.a. residues in the CaMS had differential effects in NCX1.1 and NCX1.3. Mutating the first two conserved a.a. in NCX1.1 decreased exchange activity; mutating the 3rd or 4th conserved a.a. residues did not alter exchange activity, but CaM co-expression suppressed activity. Mutating the 2nd and 3rd conserved a.a. residues in NCX1.3 decreased exchange activity. Taken together, our results demonstrate that CaM senses changes in [Ca2+]i and binds to the cytoplasmic loop of NCX1 to regulate exchange activity.
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