Jennifer M. Johnston

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Several G protein-coupled receptors (GPCRs), including opioid receptors deltaOR, muOR, and kappaOR, have been reported to form stable dimers or oligomers in lipid bilayers and cell membranes. This notion has been recently challenged by imaging data supporting a transient nature of GPCR association. Here we use umbrella sampling reconstructed free energies(More)
Expression of pituitary adenylate cyclase-activating polypeptide in sensory neurons varies with injury or inflammation. The neurotrophins NGF and NT-3 are profound regulators of neuronal peptidergic phenotype in intact and injured sensory neurons. This study examined their potential for modulation of PACAP expression in adult rat with intact and injured(More)
Targeting of dorsal root ganglia by diabetes could account for the selective sensory abnormalities that patients with early diabetic polyneuropathy develop. In this work, we addressed survival, phenotype and gene expression in sensory neurones in lumbar dorsal root ganglia in a long-term model of experimental streptozotocin-induced diabetes in rats,(More)
Neurotrophins exert effects on sensory neurons through receptor tyrosine kinases (trks) and a common neurotrophin receptor (p75). Quantitative in situ hybridization studies were performed on serial sections to identify neurons expressing single or multiple neurotrophin trk receptor mRNA(s) in adult lumbar dorsal root ganglion (DRG) in order to examine the(More)
Considerable evidence has accumulated in recent years suggesting that G protein-coupled receptors (GPCRs) associate in the plasma membrane to form homo- and/or heteromers. Nevertheless, the stoichiometry, fraction and lifetime of such receptor complexes in living cells remain topics of intense debate. Motivated by experimental data suggesting differing(More)
Opioid receptors, like other members of the G protein-coupled receptor (GPCR) family, have been shown to associate to form dimers and/or oligomers at the plasma membrane. Whether this association is stable or transient is not known. Recent compelling evidence suggests that at least some GPCRs rapidly associate and dissociate. We have recently calculated(More)
The recent mu-opioid receptor (MOPr) and kappa-opioid receptor (KOPr) crystal structures have inspired hypotheses of physiologically relevant dimerization contacts, specifically: a closely packed interface involving transmembrane (TM) helices TM5 and TM6, and a less compact interface, involving TM1, TM2, and helix 8 (H8). While the former was only found in(More)
Spatial organization of G-protein coupled receptors (GPCRs) into dimers and higher order oligomers has been demonstrated in vitro and in vivo. The pharmacological readout was shown to depend on the specific interfaces, but why particular regions of the GPCR structure are involved, and how ligand-determined states change them remains unknown. Here we show(More)
The majority of biological processes mediated by G Protein-Coupled Receptors (GPCRs) take place on timescales that are not conveniently accessible to standard molecular dynamics (MD) approaches, notwithstanding the current availability of specialized parallel computer architectures, and efficient simulation algorithms. Enhanced MD-based methods have started(More)
We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine(More)