TABLE 1.
S1R binding partners and biological outcomes mediated by these interactions.
| S1R-interactng protein | Method(s) revealing interaction | Regulation by S1R expression level | Regulation by S1R activation | References |
| Plasmalemmal ion channels | ||||
| Kv1.2 | Co-IP | Increased surface expression | Agonists (cocaine) enhanced association between S1R and Kv1.2; increased surface expression | Kourrich et al., 2013; Delint-Ramirez et al., 2018 |
| Kv1.3 | Co-IP | Co-expression increased Kv1.3 inactivation | Inhibition by SKF-10047 | Kinoshita et al., 2012 |
| Kv1.4 | Co-IP | Overexpression of S1R dose-dependently increased Kv1.4 inactivation | SKF-10047 reduced Kv1.4 outward currents | Aydar et al., 2002 |
| Kv1.5 | Overexpression of S1R inhibited Kv1.5 currents | SKF-10047 reduced Kv1.5 outward currents | Maurice et al., 2006a | |
| Kv2.1 | Imaging | Mavlyutov et al., 2010 | ||
| L-type Ca2+ channels | Co-IP | Inhibition by S1R agonists (SKF-10047) | Church and Fletcher, 1995; Zhang and Cuevas, 2002; Tchedre et al., 2008; Mueller et al., 2013 | |
| N-type Ca channels | Co-IP | Inhibition by S1R overexpression | Inhibition by SKF-10047, PRE-084 | Zhang and Cuevas, 2002; Johannessen et al., 2009; Gao et al., 2012; Zhang et al., 2017 |
| Nav1.5 | Co-IP, pulldown, AFM | Knockdown decreased Nav1.5 currents | Agonists (PTZ) promoted dissociation of Nav1.5 | Balasuriya et al., 2012 |
| ASIC1a | Co-IP, pulldown, AFM | S1R activation decreased ASIC1a currents | Herrera et al., 2008; Carnally et al., 2010 | |
| hERG | Co-IP, AFM | Potentiation by S1R overexpression | Ligands depressed hERG currents | Crottes et al., 2011; Balasuriya et al., 2014 |
| STIM1/Orai1 | Co-IP, imaging, AFM | Overexpression inhibited SOC; S1R KD enhanced SOC | Agonists inhibited SOC while antagonists enhanced SOC | Srivats et al., 2016 |
| ER channels | ||||
| InsP3R1 | Calcium imaging | Agonists suppressed ER calcium release mediated by InsP3R1 | Ryskamp et al., 2017 | |
| InsP3R3 | Co-IP | Stabilization by S1R, overexpression increased IP3-induced Ca-release | Activation of IP3-induced Ca-release by agonists | Hayashi and Su, 2007; Wu and Bowen, 2008; Delint-Ramirez et al., 2018 |
| ER resident proteins | ||||
| BiP/GRP78 | Co-IP, pull-down, NMR | Stable complex formation with BiP | Agonists dissociated S1R from BiP | Hayashi and Su, 2007; Ortega-Roldan et al., 2013 |
| Insig1; UDP-galactose:Ceramide Galactosyltransferase (CGalT) | Co-IP | Overexpression of S1R increased degradation of CGalT; S1R KO increased protein levels of CGalT | Agonist (PTZ) increased association of S1R with Insig1 | Hayashi et al., 2012 |
| IRE1a | Co-IP, proximity biotinylation labeling | S1R overexpression sustained IRE1 phosphorylation and signaling (Mori et al., 2013), S1R KO increased IRE1 activity (Rosen et al., 2019) | Fluvoxamine led to anti-inflammatory response | Hayashi and Su, 2007; Mori et al., 2013; Alam et al., 2017; Rosen et al., 2019 |
| Ankyrin | Co-IP | S1R forms stable ternary complex with ankyrin and IP3R3s | Agonists dissociated ankyrin from S1R and potentiated IP3-induced Ca-release | Hayashi and Su, 2001 |
| PM receptors/proteins | ||||
| CB1R | Bimolecular fluorescence complementation assay | S1R regulates formation of a CB1-HINT1-GluN1 complex | S1R opposed CB1R-mediated suppression of NMDAR activity | Sanchez-Blazquez et al., 2014 |
| D1R | BRET | Formation of D1R-S1R heteromers | S1R agonists enhanced D1R signaling | Navarro et al., 2010 |
| D2R | Co-IP, BRET | Formation of D2R-S1R heteromers | S1R agonist (cocaine) inhibited D2R signaling | Navarro et al., 2013 |
| MOR | Co-IP, [35S]GTPγS binding | Potentiation by S1R knockdown | Potentiation by S1R antagonist | Kim et al., 2010 |
| Integrin b1 | Co-IP | n/d | Agonist (SKF-10047) reduced interaction and reduced cell adhesion | Palmer et al., 2007 |
| BDNF | Knockdown suppressed secretion of mature BDNF | Agonists promote secretion of mature BDNF | Fujimoto et al., 2012 | |
| TrkB | Co-IP | Activation of S1R promoted TrkB signaling | Kimura et al., 2013; Ka et al., 2016 | |
| PDGFR | Pull-down, co-IP, FRET | Yao et al., 2011 | ||
| Dopamine transporter (DAT) | Co-IP, BRET, functional assays | Agonists modulated stimulant binding to DAT and stimulant-evoked DA efflux via DAT and calcium signals | Hong W.C. et al., 2017; Sambo et al., 2017 | |
| Mitochondrial proteins | ||||
| VDAC2; StAR | Co-IP | Reduction of cholesterol efflux under S1R KD conditions | Marriott et al., 2012 | |
| Proteins in the Cytosol | ||||
| Rac1 | Co-IP | Interacts as part of multiprotein complex involving S1R, IP3R, Rac, BiP | Agonist (PTZ) increased association | Natsvlishvili et al., 2015 |
| ELMOD 1-2 | Co-IP | Binding inhibited GAP activity | Ivanova et al., 2014 | |
| Other | ||||
| Emerin | Co-IP, native gel electrophoresis | Association with HDAC1/2, BAF, Emerin | Increased association with HDAC1/2, BAF, emerin after cocaine treatment (in vivo) | Tsai et al., 2015a |
| Androgen receptor (AR) | Co-IP | Increased AR degradation under S1R KD conditions | S1R inhibitors prevented nuclear transclocation and increased degradation of AR | Thomas et al., 2017 |