Interaction Between the μ Opioid Receptor and Filamin A Is Involved in Receptor Regulation and Trafficking

Onoprishvili, Irma; Andria, Matthew L.; Kramer, H. Kenneth; Ancevska-Taneva, Natasa; Hiller, Jacob M.; Simon, Eric J.

doi:10.1124/mol.64.5.1092

Cited by 92 publications

(92 citation statements)

References 35 publications

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“…There are many examples of association of the GPCRs, including MOP with other proteins, such as beta-arrestins, (Lefkowitz, 1998), GRKs (Pitcher et al, 1998) and small G proteins (Mitchell et al, 1998). Different laboratories, including ours, have reported interaction of MOP C-tail with different proteins, such as periplakin (Feng et al, 2003), Phospholipase D2 (Koch et al, 2003), mPKCI (Guang et al, 2004), HSP40 {Ancevska-Taneva, 2006 #5292)and Filamin A (Onoprishvili et al, 2003).…”

Section: Introductionmentioning

confidence: 85%

“…These cells were used for all studies. The affinity (K D ) and B MAX of the nonselective opioid antagonist [ 3 H]diprenorphine and of the mu agonist [ 3 H]DAMGO were very similar in the A7 and M2 cell lines expressing MOP (Onoprishvili et al, 2003). Chronic treatment of melanoma cells with morphine caused a concentration and time-dependent change in MOP density as determined by radioligand binding assays using [ 3 H]diprenorphine.…”

Section: Regulation Of Mop Binding In Melanoma Cellsmentioning

confidence: 98%

“…We have reported (Onoprishvili et al, 2003) the finding that filamin A binds to the carboxyl tail of the MOP. This interaction drastically reduces the effects of chronic treatment with mu agonist, such as down-regulation, desensitization and trafficking of the MOP, as shown in the melanoma cell line M2, which does not express endogenous filamin A.…”

Section: Introductionmentioning

confidence: 98%

“…Filamin A is known to bind to various membrane and signaling molecules, see reviews (Stossel et al, 2001;van der Flier and Sonnenberg, 2001)}. More recently different laboratories, including our own, demonstrated that filamin A associates with various GPCRs, such as the D2 and D3 dopamine receptors (Li et al, 2000;Lin et al, 2001), the calcium-sensing receptor (CaR) (Awata et al, 2001;Hjalm et al, 2001), the metabotropic glutamate receptor type 7 (Enz, 2002), alpha1-adrenergic receptors (Zhang et al, 2004), calcitonin receptor (Seck et al, 2003) and the mu opioid receptor (MOP) (Onoprishvili et al, 2003). In some cases, such as the calcium sensing receptor and the MOP, the binding of filamin A is to the carboxyl tail, while for other receptors, such as the D2 and D3 dopamine receptors, the binding is to the third cytoplasmic loop.…”

Section: Introductionmentioning

confidence: 99%

“…Our previously reported studies on the filamin A-MOP interaction (Onoprishvili et al, 2003) were carried out exclusively with the synthetic mu-selective peptide agonist DAMGO. The current study was designed to test the effect of morphine, as well as other opioids, in the cell line lacking filamin A (M2) and compare them with effects in a subclone of the cell line (A7), expressing filamin A.…”

Section: Introductionmentioning

confidence: 99%

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Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Onoprishvili

Simon

2007

Brain Research

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We investigated the effects of morphine and other agonists on the human mu opioid receptor (MOP) expressed in M2 melanoma cells, lacking the actin cytoskeleton protein filamin A and in A7, a sub clone of the M2 melanoma cells, stably transfected with filamin A cDNA. The results of binding experiments showed, that after chronic morphine treatment (24 hr) of A7 cells, MOP binding sites were down-regulated to 63% of control, whereas, unexpectedly, in M2 cells, MOP binding was upregulated to 188% of control naïve cells. Similar up-regulation was observed with the agonists methadone and levorphanol. The presence of antagonists (naloxone or CTAP) during chronic morphine treatment inhibited MOP down-regulation in A7 cells. In contrast, morphine-induced upregulation of MOP in M2 cells was further increased by these antagonists. Chronic morphine desensitized MOP in A7 cells, i.e. it decreased DAMGO-induced stimulation of GTPγS binding. In M2 cells DAMGO stimulation of GTPγS binding was significantly greater than in A7 cells and was not desensitized by chronic morphine. Pertussis toxin treatment abolished morphine-induced receptor up-regulation in M2 cells, whereas it had no effect on morphine-induced down-regulation in A7 cells. These results indicate that, in the absence of filamin A, chronic treatment with morphine, methadone or levorphanol leads to up-regulation of MOP, to our knowledge, the first instance of opioid receptor up-regulation by agonists in cell culture.

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Section: Introductionmentioning

confidence: 85%

Section: Regulation Of Mop Binding In Melanoma Cellsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Onoprishvili

Simon

2007

Brain Research

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Distinct regional and subcellular localization of the actin‐binding protein filamin a in the mature rat brain

Noam

Phan

McClelland

et al. 2012

J of Comparative Neurology

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Filamin A (FLNa) is an actin-binding protein that regulates cell motility, adhesion, and elasticity by cross-linking filamentous actin. Additional roles of FLNa include regulation of protein trafficking and surface expression. Although the functions of FLNa during brain development are well studied, little is known on its expression, distribution, and function in the adult brain. Here we characterize in detail the neuroanatomical distribution and subcellular localization of FLNa in the mature rat brain, by using two antisera directed against epitopes at either the N′ or the C′ terminus of the protein, further validated by mRNA expression. FLNa was widely and selectively expressed throughout the brain, and the intensity of immunoreactivity was region dependent. The most intensely FLNa-labeled neurons were found in discrete neuronal systems, including basal forebrain structures, anterior nuclear group of thalamus, and hypothalamic parvocellular neurons. Pyramidal neurons in neocortex and hippocampus and magnocellular cells in basolateral amygdaloid nucleus were also intensely FLNa immunoreactive, and strong FLNa labeling was evident in the pontine and medullary raphe nuclei and in sensory and spinal trigeminal nuclei. The subcellular localization of FLNa was evaluated in situ as well as in primary hippocampal neurons. Punctate expression was found in somata and along the dendritic shaft, but FLNa was not detected in dendritic spines. These subcellular distribution patterns were recapitulated in hippocampal and neocortical pyramidal neurons in vivo. The characterization of the expression and subcellular localization of FLNa may provide new clues to the functional roles of this cytoskeletal protein in the adult brain.

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Activity‐regulated cytoskeleton‐associated protein arc is targeted to dendrites and coexpressed with mu‐opioid receptors in postnatal rat caudate‐putamen nucleus

Wang

Pickel

2004

J of Neuroscience Research

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Dendritic expression of the activity-regulated cytoskeleton-associated protein (Arc) is dramatically enhanced by increased synaptic activity in adult brain. We used immunocytochemical electron microscopy to determine whether the subcellular localization of Arc in developing dendrites corresponds to the peak period of synaptogenesis in the postnatal rat caudate-putamen nucleus (CPN). The distribution was compared with that of mu-opioid receptors (MORs), whose localization in dendritic spines closely parallels excitatory synapse formation during postnatal development (Wang et al. [2003] Neuroscience 118:695-708). Sections were processed for immunocytochemical detection of antisera against Arc or MORs at the beginning (postnatal day 15; P15) and the end (P30) of the peak period of synaptogenesis in rat CPN. At P15, immunolabeling for Arc showed a punctate distribution in the cytoplasm of dendritic shafts, some of which was associated with polyribosomes. In some spiny dendrites, Arc immunoreactivity was more intensely localized in putative spines than in their parental dendrites, whereas, in other spiny dendrites, Arc labeling was restricted in the shafts. Many dendritic shafts and spines also showed immunoreactivity for MORs, although dually labeled spines were less numerous than the shafts. At P30, the proportion of singly and dually labeled spines significantly increased from 2.0% to 7.5% and from 9.5% to 21%, respectively. Arc labeling in spines was more detectable beneath the postsynaptic density or at extrasynaptic sites on the plasma membrane. Our results suggest a correlation between Arc expression in dendritic spines during postnatal development and the onset of synaptogenesis in opioid-responsive neurons in the rat CPN.

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Interaction Between the μ Opioid Receptor and Filamin A Is Involved in Receptor Regulation and Trafficking

Cited by 92 publications

References 35 publications

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Distinct regional and subcellular localization of the actin‐binding protein filamin a in the mature rat brain

Activity‐regulated cytoskeleton‐associated protein arc is targeted to dendrites and coexpressed with mu‐opioid receptors in postnatal rat caudate‐putamen nucleus

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