Beyond Store Depletion: A Distinct Origin of STIM1 Oscillations

Are Ca²⁺ Oscillations Driven by Cytoplasmic or Membrane Oscillators?

Current models of Ca²⁺ oscillations are largely based on oscillatory ER Ca²⁺ release through calcium-induced calcium release (CICR). Yet direct evidence for periodic ER Ca²⁺ depletion under physiological conditions remains lacking, leaving the relationship between ER Ca²⁺ dynamics and cytosolic Ca²⁺ oscillations an open question.

This study investigated whether the oscillatory behavior of STIM1 (stromal interaction molecule 1), a protein involved in calcium (Ca²⁺) signaling, and endoplasmic reticulum (ER)-plasma membrane (PM) contact site dynamics, are autonomous mechanisms driving calcium oscillations in mast cells.

Calcium oscillations are vital for many cellular processes, such as gene expression, secretion, and actin dynamics. Understanding the mechanisms behind these oscillations could improve treatments for immune and secretory disorders, where calcium signaling plays a key role.

These findings point to a new paradigm for Ca²⁺ signaling in which cortical excitability emerges from dynamic membrane-associated processes rather than intracellular regulation, with important implications for information processing and signaling in nonexcitable and likely excitable cells.

The authors propose further research into the molecular mechanisms governing ER-PM contact site dynamics and their role in calcium signaling.