Stromal interaction molecule 1–Transient receptor potential cation channel subfamily C member 1 complex (STIM1–TRPC1)

The STIM1–TRPC1 complex is a fundamental component of the store-operated calcium entry (SOCE) machinery, a process essential for maintaining intracellular calcium homeostasis. Stromal interaction molecule 1 (STIM1) functions as a calcium sensor within the endoplasmic reticulum (ER) lumen; upon depletion of ER calcium stores, STIM1 undergoes a conformational change, oligomerizes, and translocates to ER-plasma membrane junctions [1, 3]. At these junctions, STIM1 physically interacts with and activates the Transient receptor potential cation channel subfamily C member 1 (TRPC1), often in coordination with Orai1, to facilitate the influx of extracellular calcium [2, 5]. This calcium entry is vital for diverse physiological processes, including gene transcription, cell cycle progression, and contractile function in muscle cells [4, 6]. Dysregulation of the STIM1–TRPC1 complex is heavily implicated in various pathologies, such as cardiac hypertrophy, where overactive SOCE drives pathological remodeling, and in several cancers where it promotes tumor cell migration and survival [2, 7]. Consequently, this complex represents a significant therapeutic target, with research focusing on small-molecule inhibitors that can selectively disrupt the STIM1–TRPC1 interaction or block the resulting calcium current to treat inflammatory and proliferative diseases [8].

Other names

SOCE machineryStore-operated calcium entry complexSTIM1-TRPC1-Orai1 ternary complexTRPC1-STIM1 signaloplex

Inhibition of store-operated calcium entry by blocking the physical interaction between STIM1 and TRPC1 or by direct antagonism of the TRPC1 channel pore [8, 10].