International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Regulatory mechanisms of the store-operated Ca2+ entry through Orai1 and STIM1 by an adaptor protein in non-excitable cells

  • Kang, Jung Yun (Department of Dental Hygiene, College of Software Digital Healthcare Convergence, Yonsei University) ;
  • Yang, Yu-Mi (Department of Oral Biology, Yonsei University College of Dentistry)
  • Received : 2022.09.13
  • Accepted : 2022.09.19
  • Published : 2022.09.30
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Abstract

Store-operated Ca2+ entry (SOCE) represents one of the major Ca2+ entry routes in non-excitable cells. It is involved in a variety of fundamental biological processes and the maintenance of Ca2+ homeostasis. The Ca2+ release-activated Ca2+ (CRAC) channel consists of stromal interaction molecule and Orai; however, the role and action of Homer proteins as an adaptor protein to SOCE-mediated Ca2+ signaling through the activation of CRAC channels in non-excitable cells still remain unknown. In the present study, we investigated the role of Homer2 in the process of Ca2+ signaling induced by the interaction between CRACs and Homer2 proteins in non-excitable cells. The response to Ca2+ entry by thapsigargin-mediated Ca2+ store depletion remarkably decreased in pancreatic acinar cells of Homer2-/- mice, as compared to wild-type cells. It also showed critical differences in regulated patterns by the specific blockers of SOCE in pancreatic acinar cells of Homer2-/- mice. The response to Ca2+ entry by the depletion in Ca2+ store markedly increased in the cellular overexpression of Orai1 and STIM1 as compared to the overexpression of Homer2 in cells; however, this response was remarkably inhibited by the overexpression of Orai1, STIM1, and Homer2. These results suggest that Homer2 has a critical role in the regulatory action of SOCE activity and the interactions between CRAC channels.

Keywords

Acknowledgement

이 논문은 정부(과학기술정보통신부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구임(NRF-2015R1D1A1A01057277; NRF-2020R1A2C1004942; NRF-2022R1G1A1004843).

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