The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Jennifer L Whistler - One of the best experts on this subject based on the ideXlab platform.
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the role of mu opioid receptor desensitization and Endocytosis in morphine tolerance and dependence
Current Opinion in Neurobiology, 2007Co-Authors: Lene Martini, Jennifer L WhistlerAbstract:Following activation, most G protein coupled receptors undergo regulation by a cascade of events that promote receptor desensitization and Endocytosis. Following Endocytosis, receptors can then be recycled to the plasma membrane, retained in an intracellular compartment, or targeted for degradation. For receptors that are recycled, like the mu opioid receptor (MOR), Endocytosis serves as the first step toward resensitizing receptors. For receptors that are degraded, Endocytosis serves as the first step toward receptor downregulation. Thus, for receptors like the MOR, the desensitization–Endocytosis–resensitization cycle serves as a rapid and dynamic means to titrate signaling through the receptor. However, not all agonist ligands at the MOR promote the same degree of receptor desensitization and Endocytosis. For example, the endogenous peptide ligands at the MOR induce rapid desensitization, Endocytosis, and recycling. By contrast, morphine induces only weak or partial desensitization and little to no Endocytosis. As a consequence, signal transduction promoted by morphine is less dynamic than that induced by endogenous ligands as well as other opioid agonists that promote Endocytosis. The resulting imbalance of desensitization–Endocytosis–resensitization has at least two consequences: (1) in cell types where morphine induces desensitization but not Endocytosis and/or resensitization, desensitization is protracted; (2) in cell types where morphine induces neither desensitization nor Endocytosis, prolonged signaling through the receptor leads to multiple cellular adaptations downstream of receptor-G protein coupling. Both protracted desensitization and adaptive cellular changes probably contribute to the pronounced in vivo tolerance and dependence that occur with chronic morphine treatment. As a consequence, facilitating receptor Endocytosis, using either genetic or pharmacological approaches, can restore the balance of signaling through the receptor and affect the development of tolerance and dependence.
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Endocytosis of the mu opioid receptor reduces tolerance and a cellular hallmark of opiate withdrawal
Neuron, 2001Co-Authors: Andrew K Finn, Jennifer L WhistlerAbstract:Abstract Morphine is unusual in its failure to promote robust desensitization and Endocytosis of the mu opioid receptor (MOR), processes that for many receptors contribute directly to tolerance. This apparent paradox has led us to revise the idea that receptor desensitization and Endocytosis are solely responsible for tolerance and withdrawal to morphine, and instead test the hypothesis that these side effects occur due to abnormally prolonged MOR signaling. We report here that MOR mutations that facilitate Endocytosis reduce the development of cellular tolerance and cAMP superactivation, a cellular hallmark of withdrawal. Moreover, mutant receptors with reduced Endocytosis produce exacerbated superactivation. These data demonstrate a critical role for receptor Endocytosis in the development of adverse side effects associated with prolonged opiate use.
Kathryn R. Ayscough - One of the best experts on this subject based on the ideXlab platform.
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Functions of actin in Endocytosis
Cellular and Molecular Life Sciences, 2009Co-Authors: Alastair S. Robertson, Elizabeth Smythe, Kathryn R. AyscoughAbstract:Endocytosis is a fundamental eukaryotic process required for remodelling plasma-membrane lipids and protein to ensure appropriate membrane composition. Increasing evidence from a number of cell types reveals that actin plays an active, and often essential, role at key endocytic stages. Much of our current mechanistic understanding of the endocytic process has come from studies in budding yeast and has been facilitated by yeast’s genetic amenability and by technological advances in live cell imaging. While Endocytosis in metazoans is likely to be subject to a greater array of regulatory signals, recent reports indicate that spatiotemporal aspects of vesicle formation requiring actin are likely to be conserved across eukaryotic evolution. In this review we focus on the ‘modular’ model of Endocytosis in yeast before highlighting comparisons with other cell types. Our discussion is limited to Endocytosis involving clathrin as other types of Endocytosis have not been demonstrated in yeast.
Sojin Shikano - One of the best experts on this subject based on the ideXlab platform.
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differential phosphorylation signals control Endocytosis of gpr15
Molecular Biology of the Cell, 2017Co-Authors: Yukari Okamoto, Sojin ShikanoAbstract:: GPR15 is an orphan G protein-coupled receptor (GPCR) that serves for an HIV coreceptor and was also recently found as a novel homing receptor for T-cells implicated in colitis. We show that GPR15 undergoes a constitutive Endocytosis in the absence of ligand. The Endocytosis was clathrin dependent and partially dependent on β-arrestin in HEK293 cells, and nearly half of the internalized GPR15 receptors were recycled to the plasma membrane. An Ala mutation of the distal C-terminal Arg-354 or Ser-357, which forms a consensus phosphorylation site for basophilic kinases, markedly reduced the Endocytosis, whereas phosphomimetic mutation of Ser-357 to Asp did not. Ser-357 was phosphorylated in vitro by multiple kinases, including PKA and PKC, and pharmacological activation of these kinases enhanced both phosphorylation of Ser-357 and Endocytosis of GPR15. These results suggested that Ser-357 phosphorylation critically controls the ligand-independent Endocytosis of GPR15. The functional role of Ser-357 in Endocytosis was distinct from that of a conserved Ser/Thr cluster in the more proximal C-terminus, which was responsible for the β-arrestin- and GPCR kinase-dependent Endocytosis of GPR15. Thus phosphorylation signals may differentially control cell surface density of GPR15 through Endocytosis.
David A Foster - One of the best experts on this subject based on the ideXlab platform.
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role for phospholipase d in receptor mediated Endocytosis
Molecular and Cellular Biology, 2001Co-Authors: Yingjie Shen, Lizhong Xu, David A FosterAbstract:In response to epidermal growth factor (EGF), the EGF receptor is endocytosed and degraded. A substantial lag period exists between Endocytosis and degradation, suggesting that Endocytosis is more than a simple negative feedback. Phospholipase D (PLD), which has been implicated in vesicle formation in the Golgi, is activated in response to EGF and other growth factors. We report here that EGF receptor Endocytosis is dependent upon PLD and the PLD1 regulators, protein kinase C α and RalA. EGF-induced receptor degradation is accelerated by overexpression of either wild-type PLD1 or PLD2 and retarded by overexpression of catalytically inactive mutants of either PLD1 or PLD2. EGF-induced activation of mitogen-activated protein kinase, which is dependent upon receptor Endocytosis, is also dependent upon PLD. These data suggest a role for PLD in signaling that facilitates receptor Endocytosis.
Alastair S. Robertson - One of the best experts on this subject based on the ideXlab platform.
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Functions of actin in Endocytosis
Cellular and Molecular Life Sciences, 2009Co-Authors: Alastair S. Robertson, Elizabeth Smythe, Kathryn R. AyscoughAbstract:Endocytosis is a fundamental eukaryotic process required for remodelling plasma-membrane lipids and protein to ensure appropriate membrane composition. Increasing evidence from a number of cell types reveals that actin plays an active, and often essential, role at key endocytic stages. Much of our current mechanistic understanding of the endocytic process has come from studies in budding yeast and has been facilitated by yeast’s genetic amenability and by technological advances in live cell imaging. While Endocytosis in metazoans is likely to be subject to a greater array of regulatory signals, recent reports indicate that spatiotemporal aspects of vesicle formation requiring actin are likely to be conserved across eukaryotic evolution. In this review we focus on the ‘modular’ model of Endocytosis in yeast before highlighting comparisons with other cell types. Our discussion is limited to Endocytosis involving clathrin as other types of Endocytosis have not been demonstrated in yeast.