scholarly journals μ-Opioid Receptor Cell Surface Expression Is Regulated by Its Direct Interaction with Ribophorin I

2009 ◽  
Vol 75 (6) ◽  
pp. 1307-1316 ◽  
Author(s):  
Xin Ge ◽  
Horace H. Loh ◽  
Ping-Yee Law
Keyword(s):  
Cell Surface ◽  
Opioid Receptor ◽  
Receptor Cell ◽  
Direct Interaction ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Μ Opioid Receptor

scholarly journals Regulation of GIP and GLP1 Receptor Cell Surface Expression by N-Glycosylation and Receptor Heteromerization

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e32675 ◽  
Author(s):  
Gina M. Whitaker ◽  
Francis C. Lynn ◽  
Christopher H. S. McIntosh ◽  
Eric A. Accili
Keyword(s):  
Cell Surface ◽  
Receptor Cell ◽  
Surface Expression ◽  
Cell Surface Expression

scholarly journals Individual cells traffic the Vasopressin 2 Receptor to their cell surface with different success

2021 ◽  
Author(s):  
Eline J Koers ◽  
Bradley A Morgan ◽  
Iain B Styles ◽  
Dmitry J Veprintsev
Keyword(s):  
Cell Surface ◽  
Receptor Cell ◽  
Surface Expression ◽  
G Protein Coupled Receptors ◽  
Cell Surface Expression ◽  
Subcellular Localisation ◽  
Equal Distribution ◽  
Mutant Receptors ◽  
G Protein Coupled ◽  
Correct Expression

G protein coupled receptors (GPCRs) translate the actions of hormones and neurotransmitters into intracellular signalling events. Mutations in GPCRs can prevent their correct expression and trafficking to the cell surface and cause disease. Single cell subcellular localisation measurements reveal that while some cells appear to traffic the majority of the vasopressin 2 receptor (V2R) molecules to the cell surface, others retain a greater number of receptors in the ER or have approximately equal distribution. Mutations in the V2R affect the proportion of cells able to send this GPCR to their cell surface but surprisingly they do not prevent all cells from correctly trafficking the mutant receptors. These findings reveal the potential for rescue of mutant receptor cell surface expression by pharmacological manipulation of the GPCR folding and trafficking machinery.

scholarly journals Investigating the Effects of Novel Kappa Opioid Receptor Agonists on the Dopamine Transporter

2021 ◽  
Author(s):  
◽  
Bridget Simonson
Keyword(s):  
Cell Surface ◽  
Dopamine Transporter ◽  
Opioid Receptor ◽  
Serotonin Transporter ◽  
Surface Expression ◽  
Kappa Opioid Receptor ◽  
Cell Surface Expression ◽  
Salvinorin A ◽  
Kappa Opioid ◽  
Opioid Receptor Agonists

<p>Classic kappa opioid receptor (KOPr) agonists have shown anti-addictive properties in rat models of addiction (Heidbreder et al. 1998; Schenk et al. 1999; Sun et al. 2010), and this has been shown to be partially through modulation of dopamine and serotonin in the synapse (Thompson et al. 2000; Zhang et al. 2004; Zakharova et al. 2008a). However, they have side effects such as depression and dysphoria and therefore have not been moved into the clinic. The novel KOPr agonist salvinorin A has a completely different structure compared to the classic agonists, and along with its novel analogues has opened up a new family of KOPr agonists which may possess anti-addictive properties and have the potential to have decreased side effects. Salvinorin A has also demonstrated anti-addictive properties (Morani et al. 2009). In this study the novel KOPr agonist salvinorin A and its analogues DS-1-240 and DS-3-216 were investigated, along with the classic agonists U50,488H and U69,593. Their effects on the dopamine transporter (DAT) were measured using isolated rat brain tissue and cell models. The effects of U50,488H and salvinorin A on the serotonin transporter (SERT) was also measured in rat striatum using rotating disk electrode voltammetry, which was established to measure serotonin uptake in our lab during this study. We found that all of the kappa opioid receptor agonists studied in isolated rat brain tissue caused dose dependent increases in uptake of dopamine by the dopamine transporter and a decrease in uptake of serotonin by the serotonin transporter. The effect on the serotonin transporter was observed after a 15 min incubation with the agonists. Salvinorin A had a faster effect on the dopamine transporter than the other compounds investigated, with increases measured at 1 min rather than 4 min. DAT kinetics showed increases in Vmax for all agonists investigated, and both U69,593 and DS-1-240 also showed increased Km values. This demonstrates an overall increase in function, with the possibility of increased cell surface expression. Further investigation using cell models also found an increase in uptake of the fluorescent monoamine transporter substrate ASP+ by YFP tagged human DAT (YFP-hDAT). This effect was seen with all the agonists studied after incubations of less than 5 min and was YFP-hDAT trafficking-independent. The increase in uptake seen may be due to increased active YFP-hDAT found on the cell membrane as ASP+ binding studies demonstrated an increase in binding. The acute increase in YFP-hDAT function was found to be ERK1/2 dependent for all compounds studied, and was also dependent on intact lipid rafts in the cell membrane. After a 30 min incubation, salvinorin A and U50,488H still caused increased uptake of ASP+ by YFP-hDAT, whereas DS-1-240 and DS-3-216 did not. Increases in cell surface expression of YFP-hDATwas seen at this time point with salvinorin A, U69,593, and DS-3-216. Further investigation into this found that the increase in cell surface expression of YFP-hDAT after salvinorin A treatment was ERK1/2 dependent, whereas the increase seen with U69,593 appeared to be ERK1/2 independent. Overall, this data demonstrates that KOPr rapidly regulates DAT function by a trafficking-independent, ERK1/2-, and lipid raft-dependent mechanism. The classic KOPr agonist U50,488H and salvinorin A also caused a decrease in serotonin uptake by SERT, confirming that the KOPr also regulates SERT. The data from this study provides more information on how these classic and novel KOPr agonists function to regulate DAT and SERT, which may help explain some of the anti-addictive properties displayed by these compounds.</p>

CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression

2008 ◽  
Vol 369 (2) ◽  
pp. 603-608 ◽  
Author(s):  
Kay Maeda ◽  
Mitsuya Haraguchi ◽  
Atsuo Kuramasu ◽  
Takeya Sato ◽  
Kyohei Ariake ◽  
...  
Keyword(s):  
Cell Surface ◽  
Receptor Cell ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

scholarly journals Microbial Disease Spectrum Linked to a Novel IL-12Rβ1 N-Terminal Signal Peptide Stop-Gain Homozygous Mutation with Paradoxical Receptor Cell-Surface Expression

2017 ◽  
Vol 8 ◽  
Author(s):  
Thais Louvain de Souza ◽  
Regina C. de Souza Campos Fernandes ◽  
Juliana Azevedo da Silva ◽  
Vladimir Gomes Alves Júnior ◽  
Adelia Gomes Coelho ◽  
...  
Keyword(s):  
Cell Surface ◽  
Signal Peptide ◽  
Receptor Cell ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Homozygous Mutation ◽  
Disease Spectrum ◽  
Microbial Disease

scholarly journals P2X7 Receptor Cell Surface Expression and Cytolytic Pore Formation Are Regulated by a Distal C-terminal Region

2002 ◽  
Vol 278 (10) ◽  
pp. 8853-8860 ◽  
Author(s):  
Megan L. Smart ◽  
Ben Gu ◽  
Rekha G. Panchal ◽  
James Wiley ◽  
Brett Cromer ◽  
...  
Keyword(s):  
Cell Surface ◽  
P2x7 Receptor ◽  
Pore Formation ◽  
Receptor Cell ◽  
Surface Expression ◽  
Terminal Region ◽  
Cell Surface Expression

scholarly journals Investigating the Effects of Novel Kappa Opioid Receptor Agonists on the Dopamine Transporter

2021 ◽  
Author(s):  
◽  
Bridget Simonson
Keyword(s):  
Cell Surface ◽  
Dopamine Transporter ◽  
Opioid Receptor ◽  
Serotonin Transporter ◽  
Surface Expression ◽  
Kappa Opioid Receptor ◽  
Cell Surface Expression ◽  
Salvinorin A ◽  
Kappa Opioid ◽  
Opioid Receptor Agonists

<p>Classic kappa opioid receptor (KOPr) agonists have shown anti-addictive properties in rat models of addiction (Heidbreder et al. 1998; Schenk et al. 1999; Sun et al. 2010), and this has been shown to be partially through modulation of dopamine and serotonin in the synapse (Thompson et al. 2000; Zhang et al. 2004; Zakharova et al. 2008a). However, they have side effects such as depression and dysphoria and therefore have not been moved into the clinic. The novel KOPr agonist salvinorin A has a completely different structure compared to the classic agonists, and along with its novel analogues has opened up a new family of KOPr agonists which may possess anti-addictive properties and have the potential to have decreased side effects. Salvinorin A has also demonstrated anti-addictive properties (Morani et al. 2009). In this study the novel KOPr agonist salvinorin A and its analogues DS-1-240 and DS-3-216 were investigated, along with the classic agonists U50,488H and U69,593. Their effects on the dopamine transporter (DAT) were measured using isolated rat brain tissue and cell models. The effects of U50,488H and salvinorin A on the serotonin transporter (SERT) was also measured in rat striatum using rotating disk electrode voltammetry, which was established to measure serotonin uptake in our lab during this study. We found that all of the kappa opioid receptor agonists studied in isolated rat brain tissue caused dose dependent increases in uptake of dopamine by the dopamine transporter and a decrease in uptake of serotonin by the serotonin transporter. The effect on the serotonin transporter was observed after a 15 min incubation with the agonists. Salvinorin A had a faster effect on the dopamine transporter than the other compounds investigated, with increases measured at 1 min rather than 4 min. DAT kinetics showed increases in Vmax for all agonists investigated, and both U69,593 and DS-1-240 also showed increased Km values. This demonstrates an overall increase in function, with the possibility of increased cell surface expression. Further investigation using cell models also found an increase in uptake of the fluorescent monoamine transporter substrate ASP+ by YFP tagged human DAT (YFP-hDAT). This effect was seen with all the agonists studied after incubations of less than 5 min and was YFP-hDAT trafficking-independent. The increase in uptake seen may be due to increased active YFP-hDAT found on the cell membrane as ASP+ binding studies demonstrated an increase in binding. The acute increase in YFP-hDAT function was found to be ERK1/2 dependent for all compounds studied, and was also dependent on intact lipid rafts in the cell membrane. After a 30 min incubation, salvinorin A and U50,488H still caused increased uptake of ASP+ by YFP-hDAT, whereas DS-1-240 and DS-3-216 did not. Increases in cell surface expression of YFP-hDATwas seen at this time point with salvinorin A, U69,593, and DS-3-216. Further investigation into this found that the increase in cell surface expression of YFP-hDAT after salvinorin A treatment was ERK1/2 dependent, whereas the increase seen with U69,593 appeared to be ERK1/2 independent. Overall, this data demonstrates that KOPr rapidly regulates DAT function by a trafficking-independent, ERK1/2-, and lipid raft-dependent mechanism. The classic KOPr agonist U50,488H and salvinorin A also caused a decrease in serotonin uptake by SERT, confirming that the KOPr also regulates SERT. The data from this study provides more information on how these classic and novel KOPr agonists function to regulate DAT and SERT, which may help explain some of the anti-addictive properties displayed by these compounds.</p>

Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 243-250 ◽  
Author(s):  
Masateru Hiyoshi ◽  
Shinya Suzu ◽  
Yuka Yoshidomi ◽  
Ranya Hassan ◽  
Hideki Harada ◽  
...  
Keyword(s):  
Cell Surface ◽  
Direct Interaction ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Cell Surface Expression ◽  
Down Regulation ◽  
Critical Determinant ◽  
Src Tyrosine Kinase ◽  
Macrophage Colony ◽  
Hiv 1

Nef is a multifunctional pathogenetic protein of HIV-1, the interaction of which with Hck, a Src tyrosine kinase highly expressed in macrophages, has been shown to be responsible for the development of AIDS. However, how the Nef-Hck interaction leads to the functional aberration of macrophages is poorly understood. We recently showed that Nef markedly inhibited the activity of macrophage colony-stimulating factor (M-CSF), a primary cytokine for macrophages. Here, we show that the inhibitory effect of Nef is due to the Hck-dependent down-regulation of the cell surface expression of M-CSF receptor Fms. In the presence of Hck, Nef induced the accumulation of an immature under–N-glycosylated Fms at the Golgi, thereby down-regulating Fms. The activation of Hck by the direct interaction with Nef was indispensable for the down-regulation. Unexpectedly, the accumulation of the active Hck at the Golgi where Nef prelocalized was likely to be another critical determinant of the function of Nef, because the expression of the constitutive-active forms of Hck alone did not fully down-regulate Fms. These results suggest that Nef perturbs the intracellular maturation and the trafficking of nascent Fms, through a unique mechanism that required both the activation of Hck and the aberrant spatial regulation of the active Hck.

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