Int J Oral Biol.  2022 Sep;47(3):33-40. 10.11620/IJOB.2022.47.3.33.

Regulatory mechanisms of the store-operated Ca ²⁺ entry through Orai1 and STIM1 by an adaptor protein in non-excitable cells

• Kang JY
• Yang YM

• KMID: 2536297
• DOI: http://doi.org/10.11620/IJOB.2022.47.3.33

Abstract

Store-operated Ca ²⁺ entry (SOCE) represents one of the major Ca ²⁺ entry routes in non-excitable cells. It is involved in a variety of fundamental biological processes and the maintenance of Ca ²⁺ homeostasis. The Ca ²⁺ releaseactivated Ca ²⁺ (CRAC) channel consists of stromal interaction molecule and Orai; however, the role and action of Homer proteins as an adaptor protein to SOCE-mediated Ca ²⁺ 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 Ca ²⁺ signaling induced by the interaction between CRACs and Homer2 proteins in non-excitable cells. The response to Ca ²⁺ entry by thapsigargin-mediated Ca ²⁺ 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 Ca ²⁺ entry by the depletion in Ca ²⁺ 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.

Keyword

Calcium signaling; Ion channel gating; Orai1 protein; Stromal interaction molecule 1