Figure 3.

Contribution of neuronal STIM proteins and glutamate receptors to Ca²⁺ signaling dysregulation in TBI. The elevation of glutamate release leads to the excessive stimulation of glutamate receptors (e.g., mGluR1). mGluR1 couples to Gα-protein, which activates PLCβ and induces the formation of IP₃ that interacts with IP₃Rs, causing the release of Ca²⁺ from ER stores. mGluR1 also contributes to RyR-mediated Ca²⁺ leakage, resulting in lower ER Ca²⁺ levels, which in turn activate STIM proteins and promote SOCE that contributes to Ca²⁺ overload. Solid black arrows represent the interaction mechanisms; red solid arrows symbolize increased expression/concentration.