Differential regulation of Ca2+ influx by Orai channels mediates enamel mineralization

Miriam Eckstein, Martin Vaeth, Francisco J. Aulestia, Veronica Costiniti, Serena N. Kassam, Timothy G. Bromage, Pal Pedersen, Thomas Issekutz, Youssef Idaghdour, Amr M. Moursi, Stefan Feske, Rodrigo S. Lacruz

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

39 Citas (Scopus)

Resumen

Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane Orai proteins (Orai1, Orai2, and Orai3) leads to sustained Ca2+ fluxes that are critical for many cellular functions. Mutations in the human Orai1 gene result in immunodeficiency, anhidrotic ectodermal dysplasia, and enamel defects. In our investigation of the role of Orai proteins in enamel, we identified enamel defects in a patient with an Orai1 null mutation. Targeted deletion of the Orai1 gene in mice showed enamel defects and reduced SOCE in isolated enamel cells. However, Orai2−/− mice showed normal enamel despite having increased SOCE in the enamel cells. Knockdown experiments in the enamel cell line LS8 suggested that Orai2 and Orai3 modulated Orai1 function, with Orai1 and Orai2 being the main contributors to SOCE. Orai1-deficient LS8 cells showed altered mitochondrial respiration with increased oxygen consumption rate and ATP, which was associated with altered redox status and enhanced ER Ca2+ uptake, likely due to S-glutathionylation of SERCA pumps. Our findings demonstrate an important role of Orai1 in Ca2+ influx in enamel cells and establish a link between SOCE, mitochondrial function, and redox homeostasis.

Idioma originalEnglish
Número de artículoaav4663
PublicaciónScience Signaling
Volumen12
N.º578
DOI
EstadoPublished - 2019

Nota bibliográfica

Funding Information:
This work was funded by the National Institute of Dental and Craniofacial Research (NIH/NIDCR) awards to R.S.L. (DE025639 and DE027679) and by NIH grants to S.F. (AI097302, AI130143, and AI107448).

Publisher Copyright:
© 2019 The Authors, some rights reserved;

ASJC Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Huella

Profundice en los temas de investigación de 'Differential regulation of Ca2+ influx by Orai channels mediates enamel mineralization'. En conjunto forman una huella única.

Citar esto