Dynamin, a GTPase Involved in the Initial Stages of Endocytosis

Vallee, Richard B.; Herskovits, Jonathan S.; Aghajanian, John G.; Burgess, Christopher C.; Shpetner, Howard S.

doi:10.1002/9780470514450.ch12

Cited by 21 publications

(11 citation statements)

References 17 publications

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“…Our results also show that morphine interfered with internalization of the fluorescent dermorphin analogue, DERM‐A594, in morphine‐tolerant rats. Taken together, the results indicated that repeated morphine administration and the development of tolerance enhanced the ability of morphine to recruit dynamin, a GTPase involved in GPCR endocytosis (Herskovits et al ., ; Vallee et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Change in functional selectivity of morphine with the development of antinociceptive tolerance

Macey

Bobeck

Suchland

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEOpioids, such as morphine, are the most effective treatment for pain but their efficacy is diminished with the development of tolerance following repeated administration. Recently, we found that morphine activated ERK in opioid-tolerant but not in naïve rats, suggesting that morphine activation of μ-opioid receptors is altered following repeated morphine administration. Here, we have tested the hypothesis that μ-opioid receptor activation of ERK in the ventrolateral periaqueductal gray (vlPAG) is dependent on dynamin, a protein implicated in receptor endocytosis. EXPERIMENTAL APPROACHRats were made tolerant to repeated microinjections of morphine into the vlPAG. The effects of dynamin on ERK activation and antinociception were assessed by microinjecting myristoylated dominant-negative dynamin peptide (Dyn-DN) or a scrambled control peptide into the vlPAG. Microinjection of a fluorescent dermorphin analogue (DERM-A594) into the vlPAG was used to monitor μ-opioid receptor internalization. KEY RESULTSMorphine did not activate ERK and Dyn-DN administration had no effect on morphine-induced antinociception in saline-pretreated rats. In contrast, morphine-induced ERK activation in morphine-pretreated rats that was blocked by Dyn-DN administration. Dyn-DN also inhibited morphine antinociception. Finally, morphine reduced DERM-A594 internalization only in morphine-tolerant rats indicating that μ-opioid receptors were internalized and unavailable to bind DERM-A594. CONCLUSIONS AND IMPLICATIONSRepeated morphine administration increased μ-opioid receptor activation of ERK signalling via a dynamin-dependent mechanism. These results demonstrate that the balance of agonist signalling to G-protein and dynamin-dependent pathways is altered, effectively changing the functional selectivity of the agonist-receptor complex. LINKED ARTICLESThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 AbbreviationsDyn-DN, dominant-negative dynamin peptide; Dyn-scr, scrambled dynamin peptide; GRK, G-protein receptor kinase; vlPAG, ventrolateral periaqueductal gray IntroductionThe antinociceptive effects of opioids are limited by the development of tolerance with repeated administration. The mechanism for tolerance has been difficult to identify because many signalling adaptations correlate with the development of tolerance (Christie, 2008;Williams et al., 2013). Opioid agonist binding to μ-opioid receptors induces phosphorylation of the receptor by G-protein receptor kinases (GRKs) and recruitment of proteins, including β-arrestin and dynamin, involved in the internalization of the receptor (Goodman et al., 1996; receptor nomenclature follows Alexander et al., 2013a). Ligand-biased signalling of μ-opioid receptors (McPherson et al., 2010; Kelly, 2013a,b) has been observed where specific agonists preferentially couple to specific effectors. Few studies have addressed whether ligandbiased...

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Section: Discussionmentioning

confidence: 97%

Change in functional selectivity of morphine with the development of antinociceptive tolerance

Macey

Bobeck

Suchland

et al. 2014

British J Pharmacology

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“…Many studies used the overexpression of dominant negative mutants to explore the role of dynamin II in virus entry [39,40]. Mutation of dynamin II from 44K to 44A can inhibit GTPase activity and reduce endocytosis [41]. Cells were transfected with wild-type and mutant types of dynamin II respectively and infected with GDS01 and GDS09 strains at 24 h after transfection.…”

Section: Pedv Entry Involves Dynamin IImentioning

confidence: 99%

PEDV enters cells through clathrin-, caveolae-, and lipid raft-mediated endocytosis and traffics via the endo-/lysosome pathway

Wang

She

et al. 2020

Vet Res

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With the emergence of highly pathogenic variant strains, porcine epidemic diarrhea virus (PEDV) has led to significant economic loss in the global swine industry. Many studies have described how coronaviruses enter cells, but information on PEDV invasion strategies remains insufficient. Given that the differences in gene sequences and pathogenicity between classical and mutant strains of PEDV may lead to diverse invasion mechanisms, this study focused on the cellular entry pathways and cellular transport of the PEDV GI and GII subtype strains in Vero cells and IPEC-J2 cells. We first characterized the kinetics of PEDV entry into cells and found that the highest invasion rate of PEDV was approximately 33% in the IPEC-J2 cells and approximately 100% in the Vero cells. To clarify the specific endocytic pathways, systematic research methods were used and showed that PEDV enters cells via the clathrin-and caveolae-mediated endocytosis pathways, in which dynamin II, clathrin heavy chain, Eps15, cholesterol, and caveolin-1 were indispensably involved. In addition, lipid raft extraction assay showed that PEDV can also enter cells through lipid raft-mediated endocytosis. To investigate the trafficking of internalized PEDV, we found that PEDV entry into cells relied on low pH and internalized virions reached lysosomes through the early endosome-late endosome-lysosome pathway. The results concretely revealed the entry mechanisms of PEDV and provided an insightful theoretical basis for the further understanding of PEDV pathogenesis and guidance for new targets of antiviral drugs.© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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“…Ligand stimulation has no effect on the initial internalization rate or receptor recycling [42]. Using a range of techniques including potassium (K + ) depletion, which inhibits clathrin‐mediated endocytosis [43], and a dominant‐negative form of the dynamin GTPase, K44A dynamin II, which inhibits both clathrin‐ and caveolar‐mediated endocytosis [44], various groups have addressed the requirement for internalization in TGFβ signaling. Lu et al.…”

Section: Interconnection Between Tgfβ Signaling and Receptor Traffickmentioning

confidence: 99%

Control of transforming growth factor β signal transduction by small GTPases

et al. 2009

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The integrated roles of small GTPases in executing the transforming growth factor β (TGFβ) signaling pathway have attracted increasing attention in recent years. In this review, we summarize recent findings on TGFβ signaling during receptor endocytosis, Smad trafficking and actin cytoskeleton remodeling, and emphasize the role of small GTPases in these processes. First, we give an overview of the different endocytic routes taken by TGFβ receptors, their impact on active TGFβ signaling versus degradation and their regulation by the small GTPases Rab, RalA/Ral‐binding protein 1 and Rap2. Second, we focus on the mechanisms and regulation of Smad trafficking in the cytoplasm, through the nuclear pores and into the nucleus, and the contribution of Ran GTPase to these events. Third, we summarize the role of Rho small GTPases in early and late cytoskeleton remodeling in various cell models and diseases, and the positive and negative cross‐talk between Rho GTPases and the TGFβ/Smad pathway. The biological significance of this exciting research field, the perspectives and critical open questions are discussed.

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Dynamin, a GTPase Involved in the Initial Stages of Endocytosis

Cited by 21 publications

References 17 publications

Change in functional selectivity of morphine with the development of antinociceptive tolerance

Change in functional selectivity of morphine with the development of antinociceptive tolerance

PEDV enters cells through clathrin-, caveolae-, and lipid raft-mediated endocytosis and traffics via the endo-/lysosome pathway

Control of transforming growth factor β signal transduction by small GTPases

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