. Author manuscript; available in PMC: 2021 Oct 1.

Published in final edited form as: Curr Opin Physiol. 2020 Aug 16;17:187–196. doi: 10.1016/j.cophys.2020.08.004

Table 1.

Summary of optogenetic tools for noninvasive and precise control Ca²⁺ signals in mammals.

Names	Engineering templates	Photosensitive components	Stimulation	Activation (t_1/2, sec)	Deactivation (t_1/2, sec)	Cell / Tissue Types	Refs
Photoswitchable GPCRs and G proteins
ChR2	Channelrhodopsin-2	opsin	Blue light	~0.002	~0.01	Multiple mammalian cells, model organism, rodents and primates	7
OptoGPCR / OptoXRs	G_q-coupled α1AR	opsin	Blue/green light	N/A	N/A	HEK293 and mice	13
OptoGPCR / OptoXRs	Melanopsin	opsin	Blue light	< 10	N/A	Multiple mammalian cells and mice	47, 48
Photoactivatable RTKs
OptoRTKs	FGFR1^398–822	CRY2phr	Blue light	<30	N/A	HeLa/HUVECs	21, 22
	TrkA/B/C	CRY2phr	Blue light	<30	N/A	HeLa	24
	TrkA	DrBphP-PCM	nir	~7	~10	HeLa	25
STIM1-based GECAs
BACCS variants	STIM1^347–448	LOV2	Blue light	< 30	~30–60	HEK293T	33
	STIM1^347–448	2^*LOV2
	ORAI1 + STIM1^347–448	2^*LOV2
	dOrai + dmStim^413–514	2^*LOV2				S2
LOVS1K	STIM1^233–450	LOV2	Blue light	N/A	N/A	HeLa	34
Opto-CRAC1 variants	Mouse STIM1^336–486	LOV2	Blue light	23.4 ± 4.2	24.9 ± 4.8	HeLa and multiple cell lines	32
	Mouse STIM1^336–486	LOV2	NIR	<30	<30	BMDCs and mice
	Human STIM1^336–685	LOV2	Blue light	36.3 ± 6.4	n/a	HeLa
	chicken STIM1^262–412	LOV2	Blue light	~10	<30	Skin mesenchymal cells	35
	zebrafish STIM1^341–442	LOV2	Blue light	18.7	24.5	HeLa	36
Opto-CRAC2 variants	STIM1^233–685	iLID/SspB	Blue light	28.5 ± 3.2	48.6 ± 5.4	HeLa	31
	STIM1^233–685	CRY2_PHR/CIBN		23.4 ± 2.6	153.0 ± 26.2
	ER-tethered-STIM1^233–685	CRY2_PHR		37.8 ± 5.3	97.5 ± 16.5
OptoSTIM1 variants	STIM1^238–685	CRY2_PHR	Blue light	64.5 ± 4.8	274 ± 23.7	HeLa and multiple cell lines	4, 28
	STIM1^238–463			43.2 ± 3.8	383 ± 52.3
	STIM1^342–685			48.2 ± 5.4	344 ± 34.6
monSTIM1	STIM1^238–685	CRY2_PHR-E281A-9A	Blue light	24.8 ± 1.0	513.5 ± 25.8	HEK and neurons and mice	29
eOS1	STIM1^238–685	CRY2_PHR-E490G	Blue light	<60	<600	B3Z T cell	30
eOS1	STIM1^238–685	CRY2_PHR-E490G	Two-photon	<60	<600	In vivo CD8⁺ T dells	30
Light-switchable inhibition of Ca²⁺ signaling
OptoRGK	Rem^1–266	iLID/SspB	Blue light	3.2 ± 1.0^*	23.0 ± 2.4^*	HEK293; HL-1	37

cytosol-plasma membrane translocation

Abbreviations: BACCS, blue light-activated Ca²⁺ channel switch; BMDCs, bone marrow-derived DCs; CaM-M13, calmodulin fused with the M13 peptide; ChR2, Channelrhodopsin-2; CIBN, the N-terminal domain of CIB1; CRY2, cryptochrome2; eOS1, enhanced OptoSTIM1; FGFR1, fibroblast growth factor receptor 1; GECA, genetically encoded Ca²⁺ actuator; HUVECs, human umbilical vein endothelial cells; iLID, improved light-induced dimer (LOV2-SsrA); LOV2, light-oxygen-voltage sensing) domain; LOVS1K, LOV2 fused STIM1 fragments (233–450); monSTIM1, monster-OptoSTIM1; PACR, photoactivatable Ca²⁺ releaser; Opto-α₁AR, Optogenetic G_q-coupled α1-adrenergic receptor; Opto-CRAC, Optogenetic Ca²⁺ release-activated Ca²⁺ channel; OptoRGK, Optogenetic Ras-like GTPase Rad/Rem/Gem/Kir; Opto-RGS2, Optogenetic regulators of G-protein signaling; Opto-RTKs, Optogenetic receptor tyrosine kinases; OptoSTIM1, Optogenetic stromal interaction molecule 1; OptoXRs, optogenetic control of intracellular signal transduction; S1, somatosensory cortex; S2, Drosophila S2 cells; SP, Signal peptide of STIM1; NIR, near-infrared; TM, transmembrane domain; Trk, tropomyosin-related kinase;