Calcium signaling and endoplasmic reticulum stress

Abstract

Cellular homeostasis is essential for healthy functioning of cells and tissues as well as proper organ development and maintenance. A disruption in cellular homeostasis triggers stress responses including the unfolded protein response (UPR), an endoplasmic reticulum (ER) stress coping response. There is increasing evidence that Ca²⁺ signaling plays a pivotal role in stress responses, as Ca²⁺ is involved many cellular activities. The ER is the main Ca²⁺ storage organelle and the source of Ca²⁺ for intracellular signaling. The ER is equipped with a variety of stress sensors and contains many Ca²⁺ handling proteins that support a role for Ca²⁺ in stress sensing and in coordinating strategies required to cope with cellular stress. Maintenance of ER Ca²⁺ homeostasis is therefore vital in sustaining cellular functions especially during times of cellular stress. Here we focus on selected aspects of ER Ca²⁺ homeostasis, its links to ER stress, and activation of the ER stress coping response.

Keywords: Chaperones; Endoplasmic reticulum; Membrane contact site; Ryanodine receptor; Sarcoplasmic reticulum; Unfolded protein response.