scholarly journals A Conserved Motif for the Transport of G Protein-coupled Receptors from the Endoplasmic Reticulum to the Cell Surface

2004 ◽  
Vol 279 (29) ◽  
pp. 30741-30750 ◽  
Author(s):  
Matthew T. Duvernay ◽  
Fuguo Zhou ◽  
Guangyu Wu
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Conserved Motif ◽  
G Protein Coupled

The Endoplasmic Reticulum Ca2+-pump SERCA2b Interacts with G Protein-coupled Receptors and Enhances their Expression at the Cell Surface

2007 ◽  
Vol 371 (3) ◽  
pp. 622-638 ◽  
Author(s):  
Jussi T. Tuusa ◽  
Piia M.H. Markkanen ◽  
Pirjo M. Apaja ◽  
Anna E. Hakalahti ◽  
Ulla E. Petäjä-Repo
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

scholarly journals Mechanisms Governing the Activation and Trafficking of Yeast G Protein-coupled Receptors

1998 ◽  
Vol 9 (4) ◽  
pp. 885-899 ◽  
Author(s):  
Christopher J. Stefan ◽  
Mark C. Overton ◽  
Kendall J. Blumer
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
G Protein ◽  
G Proteins ◽  
Structural Changes ◽  
G Protein Coupled Receptors ◽  
Wild Type ◽  
Proline Residue ◽  
G Protein Coupled ◽  
Constitutively Active

We have addressed the mechanisms governing the activation and trafficking of G protein-coupled receptors (GPCRs) by analyzing constitutively active mating pheromone receptors (Ste2p and Ste3p) of the yeast Saccharomyces cerevisiae. Substitution of the highly conserved proline residue in transmembrane segment VI of these receptors causes constitutive signaling. This proline residue may facilitate folding of GPCRs into native, inactive conformations, and/or mediate agonist-induced structural changes leading to G protein activation. Constitutive signaling by mutant receptors is suppressed upon coexpression with wild-type, but not G protein coupling-defective, receptors. Wild-type receptors may therefore sequester a limiting pool of G proteins; this apparent “precoupling” of receptors and G proteins could facilitate signal production at sites where cell surface projections form during mating partner discrimination. Finally, rather than being expressed mainly at the cell surface, constitutively active pheromone receptors accumulate in post-endoplasmic reticulum compartments. This is in contrast to other defective membrane proteins, which apparently are targeted by default to the vacuole. We suggest that the quality-control mechanism that retains receptors in post-endoplasmic reticulum compartments may normally allow wild-type receptors to fold into their native, fully inactive conformations before reaching the cell surface. This may ensure that receptors do not trigger a response in the absence of agonist.

scholarly journals Understudied G Protein-Coupled Receptors in the Kidney

Nephron ◽  
2021 ◽  
pp. 1-4
Author(s):  
Nathan A. Zaidman ◽  
Jennifer L. Pluznick
Keyword(s):  
Renal Function ◽  
Cell Surface ◽  
Gene Family ◽  
G Protein ◽  
External Environment ◽  
G Protein Coupled Receptors ◽  
Surface Proteins ◽  
Cell Surface Proteins ◽  
Large Subset ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are cell surface proteins which play a key role in allowing cells, tissues, and organs to respond to changes in the external environment in order to maintain homeostasis. Despite the fact that GPCRs are known to play key roles in a variety of tissues, there are a large subset of GPCRs that remain poorly studied. In this minireview, we will summarize what is known regarding the “understudied” GPCRs with respect to renal function, and in so doing will highlight the promise represented by studying this gene family.

scholarly journals ADP-Ribosylation Factors Modulate the Cell Surface Transport of G Protein-Coupled Receptors

2010 ◽  
Vol 333 (1) ◽  
pp. 174-183 ◽  
Author(s):  
Chunmin Dong ◽  
Xiaoping Zhang ◽  
Fuguo Zhou ◽  
Huijuan Dou ◽  
Matthew T. Duvernay ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Surface Transport ◽  
Adp Ribosylation ◽  
G Protein Coupled

Oligomerisation of G-protein-coupled receptors

2001 ◽  
Vol 114 (7) ◽  
pp. 1265-1271 ◽  
Author(s):  
G. Milligan
Keyword(s):  
Energy Transfer ◽  
Cell Surface ◽  
G Protein ◽  
Living Cells ◽  
G Protein Coupled Receptors ◽  
Intact Cells ◽  
Effective Delivery ◽  
Multiple Copies ◽  
Agonist Ligands ◽  
G Protein Coupled

A range of approaches have recently provided evidence that G-protein-coupled receptors can exist as oligomeric complexes. Both homo-oligomers, comprising multiple copies of the same gene product, and hetero-oligomers containing more than one receptor have been detected. In several, but not all, examples, the extent of oligomerisation is regulated by the presence of agonist ligands, and emerging evidence indicates that receptor hetero-oligomers can display distinct pharmacological characteristics. A chaperonin-like role for receptor oligomerisation in effective delivery of newly synthesised receptors to the cell surface is a developing concept, and recent studies have employed a series of energy-transfer techniques to explore the presence and regulation of receptor oligomerisation in living cells. However, the majority of studies have relied largely on co-immunoprecipitation techniques, and there is still little direct information on the fraction of receptors existing as oligomers in intact cells.

scholarly journals Cloning, Expression, and Functional Characterization of Relaxin Receptor (Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 7) Splice Variants from Human Fetal Membranes

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1277-1294 ◽  
Author(s):  
András Kern ◽  
Daniela Hubbard ◽  
Aaron Amano ◽  
Gillian D. Bryant-Greenwood
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
G Protein ◽  
Splice Variant ◽  
Splice Variants ◽  
Dominant Negative ◽  
Fetal Membranes ◽  
Leucine Rich Repeat ◽  
G Protein Coupled ◽  
Relaxin Receptor

The relaxin receptor [leucine-rich repeat-containing G protein-coupled receptor 7 (LGR7)] belongs to the leucine-rich repeat containing G protein-coupled receptors subgroup C. Three new LGR7 splice variants have been cloned from the human fetal membranes and shown to be truncated versions of the full-length receptor, encoded by different lengths of the extracellular domain. The expression of their mRNAs has been confirmed by both qualitative and quantitative PCR and shown to be higher in the chorion and decidua before, compared with after, spontaneous labor. When HEK293 cells were transfected with each LGR7 splice variant, their proteins were retained within the endoplasmic reticulum. However, the protein for the shortest variant was also secreted into the medium. We have characterized the intracellular functions and effects of these LGR7 variants on the function of the wild-type (WT)-LGR7. In coexpression studies, each splice variant interacted directly with the WT-LGR7 and exerted a dominant-negative effect on cAMP accumulation by the WT-LGR7 after relaxin treatment. This interaction resulted in the sequestration of the WT-LGR7 inside the cells by down-regulation of its maturation and cell surface delivery. The constitutive homodimerization of WT-LGR7 has been shown here to take place in the endoplasmic reticulum, and the presence of any one of the splice variants decreased this by the formation of heterodimers with the WT-LGR7, supporting the view that homodimerization is a prerequisite for receptor trafficking to the cell surface. These data suggest that the dominant-negative effects of the LGR7 splice variants expressed in the chorion and decidua could be functionally significant in the peripartal period by inhibiting the function of WT-LGR7 and dampening the responsiveness of these tissues to endogenous relaxin.

scholarly journals Cell-Surface Receptors Transactivation Mediated by G Protein-Coupled Receptors

2014 ◽  
Vol 15 (11) ◽  
pp. 19700-19728 ◽  
Author(s):  
Fabio Cattaneo ◽  
Germano Guerra ◽  
Melania Parisi ◽  
Marta De Marinis ◽  
Domenico Tafuri ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
G Protein Coupled

scholarly journals Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors

2020 ◽  
Vol 117 (6) ◽  
pp. 2957-2967
Author(s):  
Kentaro Ikegami ◽  
Claire A. de March ◽  
Maira H. Nagai ◽  
Soumadwip Ghosh ◽  
Matthew Do ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
Surface Expression ◽  
Structural Instability ◽  
G Protein Coupled Receptors ◽  
Machine Learning Techniques ◽  
Odorant Receptors ◽  
Cell Surface Expression ◽  
Conserved Residues ◽  
G Protein Coupled

Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled receptors expressed in olfactory cilia membranes. Most odorant receptors show little to no cell surface expression in nonolfactory cells due to endoplasmic reticulum retention, which has slowed down biochemical studies. Here we provide evidence that structural instability and divergence from conserved residues of individual odorant receptors underlie intracellular retention using a combination of large-scale screening of odorant receptors cell surface expression in heterologous cells, point mutations, structural modeling, and machine learning techniques. We demonstrate the importance of conserved residues by synthesizing consensus odorant receptors that show high levels of cell surface expression similar to conventional G protein-coupled receptors. Furthermore, we associate in silico structural instability with poor cell surface expression using molecular dynamics simulations. We propose an enhanced evolutionary capacitance of olfactory sensory neurons that enable the functional expression of odorant receptors with cryptic mutations.

scholarly journals Phosphatidic acid phospholipase A1 mediates ER–Golgi transit of a family of G protein–coupled receptors

2014 ◽  
Vol 206 (1) ◽  
pp. 79-95 ◽  
Author(s):  
Govind Kunduri ◽  
Changqing Yuan ◽  
Velayoudame Parthibane ◽  
Katherine M. Nyswaner ◽  
Ritu Kanwar ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Coat Protein ◽  
Membrane Proteins ◽  
Phosphatidic Acid ◽  
G Protein ◽  
Golgi Complex ◽  
G Protein Coupled Receptors ◽  
Phospholipase A1 ◽  
Copii Vesicles ◽  
G Protein Coupled

The coat protein II (COPII)–coated vesicular system transports newly synthesized secretory and membrane proteins from the endoplasmic reticulum (ER) to the Golgi complex. Recruitment of cargo into COPII vesicles requires an interaction of COPII proteins either with the cargo molecules directly or with cargo receptors for anterograde trafficking. We show that cytosolic phosphatidic acid phospholipase A1 (PAPLA1) interacts with COPII protein family members and is required for the transport of Rh1 (rhodopsin 1), an N-glycosylated G protein–coupled receptor (GPCR), from the ER to the Golgi complex. In papla1 mutants, in the absence of transport to the Golgi, Rh1 is aberrantly glycosylated and is mislocalized. These defects lead to decreased levels of the protein and decreased sensitivity of the photoreceptors to light. Several GPCRs, including other rhodopsins and Bride of sevenless, are similarly affected. Our findings show that a cytosolic protein is necessary for transit of selective transmembrane receptor cargo by the COPII coat for anterograde trafficking.

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