A Novel Modulator of STIM2-Dependent Store-Operated Ca2+ Channel Activity

A Y Skopin; A D Grigoryev; L N Glushankova; A V Shalygin; G Wang; V G Kartzev; E V Kaznacheyeva

doi:10.32607/actanaturae.11269

A Novel Modulator of STIM2-Dependent Store-Operated Ca2+ Channel Activity

Acta Naturae. 2021 Jan-Mar;13(1):140-146. doi: 10.32607/actanaturae.11269.

Authors

A Y Skopin¹, A D Grigoryev¹, L N Glushankova¹, A V Shalygin¹, G Wang², V G Kartzev³, E V Kaznacheyeva¹

Affiliations

¹ Institute of Cytology of Russian Academy of Sciences, St. Petersburg, 194064 Russia.
² College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123 China.
³ InterBioscreen Ltd., Chernogolovka, 142432 Russia.

Abstract

Store-operated Ca²⁺ entry is one of the main pathways of calcium influx into non-excitable cells, which entails the initiation of many intracellular processes. The endoplasmic reticulum Ca²⁺ sensors STIM1 and STIM2 are the key components of store-operated Ca²⁺ entry in mammalian cells. Under physiological conditions, STIM proteins are responsible for store-operated Ca²⁺ entry activation. The STIM1 and STIM2 proteins differ in their potency for activating different store-operated channels. At the moment, there are no selective modulators of the STIM protein activity. We screened a library of small molecules and found the 4-MPTC compound, which selectively inhibited STIM2-dependent store-operated Ca²⁺ entry (IC50 = 1 μM) and had almost no effect on the STIM1-dependent activation of store-operated channels.

Keywords: 2-APB; Orai; STIM1; STIM2; calcium; store-operated Ca2+ entry.