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reach
"However, while Balasuriya et al., 2014 XREF_BIBR proposed that Sigma-1R binds to an immature hERG in the ER and reduces expression of mature hERG, Johannessen et al, 2009, suggested that sigma-1R expression enhances hERG protein maturation and stability, by regulating subunit trafficking activity of hERG XREF_BIBR."

sparser
"Our aim was to investigate the nature of the interaction between the sigma-1 receptor and hERG."

sparser
"Atomic force microscopy imaging of the isolated protein confirmed the direct binding of the sigma-1 receptor to hERG monomers, dimers, and tetramers."

sparser
"The distribution of angles between pairs of sigma-1 receptors bound to hERG tetramers had two peaks, at ∼90 and ∼180° in a ratio of ∼2:1, indicating that the sigma-1 receptor interacts with hERG with 4-fold symmetry."

sparser
"Homogeneous time-resolved fluorescence (HTRF®) allowed the detection of the interaction between the sigma-1 receptor and hERG within the plane of the plasma membrane."

sparser
"We suggest that the sigma-1 receptor may bind to hERG in the endoplasmic reticulum, aiding its assembly and trafficking to the plasma membrane."

sparser
"Atomic force imaging and homogenous time-resolved fluorescence approaches later identified that the Sig-1R interacts with hERG with a four-fold symmetry."

reach
"Mechanistically, it was observed that SIGMAR1 interacted with hERG and Kv7.1 channel in human iPSC-derived cardiomyocytes and dextromethorphan treatment modulated the interactions between SIGMAR1, hERG and K 7.1 channel, increased the plasma-membrane localization of K 7.1 and increased the gene and protein expression of K 7.1 isoform 1 in TS cardiomyocytes."

reach
"Although, to our knowledge, the interaction between SIGMAR1 and K 7.1 has not been reported previously, the direct interaction between SIGMAR1 and hERG has been studied in leukemic cells, HEK cells and neonatal rat cardiomyocytes ."

reach
"Figure 6–7) through modulating the interactions between SIGMAR1, hERG and K 7.1 channel and increasing K currents."

sparser
"The authors clarify that the direct interaction between the Sig-1R and hERG in the plasma membrane is not Sig-1R ligand-dependent but is reduced by cholesterol depletion, suggesting that Sig-1R may bind to hERG in the ER and facilitate hERG assembly and trafficking perhaps in a lipid-raft related fashion [ xref ]."

sparser
"The findings of the Sig-1R interacting with hERG in the ER and potentiating hERG maturation and translocation to the plasma membrane suggest that the Sig-1R may exert chaperoning activities in the ER to facilitate proper protein sorting to their final destinations."

sparser
"Thus, we decided to evaluate the potential interaction between SIGMAR1 and hERG channel in human iPSC-derived cardiomyocytes using PLA and examine the effect of dextromethorphan on their potential interaction."

sparser
"Inasmuch Sig1R co-immunoprecipitates with both immature and mature forms of the channel α-subunits, it is suggested that Sig1R not only associates with hERG in the ER, but also drives it to the plasma membrane (Crottes et al., xref )."

sparser
"Since progesterone is a Sig-1R antagonist, it could be hypothesized that these effects are produced through a disruption of the Sig-1R and hERG protein complexes."

sparser
"Two-hour dextromethorphan treatment significantly reduced SIGMAR1-hERG PLA signals in TS cardiomyocytes while no significant change of SIGMAR1-hERG PLA signals in the isogenic control cardiomyocytes was observed with dextromethorphan treatment at the same dose ( xref , xref and xref – xref )."

reach
"Our aim was to investigate the nature of the interaction between the sigma-1 receptor and hERG."

sparser
"Overall, these results demonstrated that SIGMAR1 directly interacted with hERG channel in human iPSC-derived cardiomyocytes and the SIGMAR1 agonist dextromethorphan might increase I Kr currents by dissociating the interaction between SIGMAR1 and hERG channel in TS cardiomyocytes, while the exact mechanisms remain to be characterized."

reach
"The distribution of angles between pairs of sigma-1 receptors bound to hERG tetramers had two peaks, at ~ 90 and ~ 180degrees in a ratio of ~ 2:1, indicating that the sigma-1 receptor interacts with hERG with 4-fold symmetry."

reach
"Homogeneous time resolved fluorescence (HTRF (R)) allowed the detection of the interaction between the sigma-1 receptor and hERG within the plane of the plasma membrane."

reach
"We suggest that the sigma-1 receptor may bind to hERG in the endoplasmic reticulum, aiding its assembly and trafficking to the plasma membrane."

sparser
"Additionally, AFM imaging and homogenous time-resolved fluorescence experiments, have demonstrated that Sig-1R interacts with hERG channels with a 4-fold symmetry in the plasma membrane of HEK293 cells stably transfected with both proteins ( xref )."

sparser
"The observation of an interaction between SIGMAR1 and hERG channel in human iPSC-derived cardiomyocytes prompted us to examine whether there is a similar interaction between SIGMAR1 and another K + channel, K V 7.1, which is encoded by KCNQ1 gene and also plays an important role in the repolarization phase of cardiac action potential as hERG channel does."

sparser
"Mechanistically, similar to what was observed in TS cardiomyocytes ( xref , xref , xref , xref ), dextromethorphan treatment significantly reduced both SIGMAR1-hERG and SIGMAR1-K V 7.1 PLA signals in the LQTS1 and LQTS2 cardiomyocytes ( xref – xref and xref – xref )."

sparser
"Although, to our knowledge, the interaction between SIGMAR1 and K V 7.1 has not been reported previously, the direct interaction between SIGMAR1 and hERG has been studied in leukemic cells, HEK cells and neonatal rat cardiomyocytes xref , xref – xref ."

sparser
"Our results confirmed the direct interaction between SIGMAR1 and hERG channel and SIGMAR1-mediated regulation of hERG channel function in human iPSC-derived cardiomyocytes while the detailed molecular mechanisms remain to be fully characterized."

reach
"Atomic force imaging and homogenous time resolved fluorescence approaches later identified that the Sig-1R interacts with hERG with a four-fold symmetry."

reach
"The authors clarify that the direct interaction between the Sig-1R and hERG in the plasma membrane is not Sig-1R ligand dependent but is reduced by cholesterol depletion, suggesting that Sig-1R may bind to hERG in the ER and facilitate hERG assembly and trafficking perhaps in a lipid-raft related fashion [XREF_BIBR]."