Filamins as integrators of cell mechanics and signalling

Stossel, Thomas P.; Condeelis, John S.; Cooley, Lynn; Hartwig, John H.; Noegel, Angelika A.; Schleicher, Michael; Shapiro, Sandor S.

doi:10.1038/35052082

Cited by 903 publications

(973 citation statements)

References 98 publications

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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: 99%

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

Onoprishvili

Simon

2007

Brain Research

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“…The susceptibility of these two structural proteins to tyrosyl radical attack may be explained by their binding to several cellular proteins, including membrane receptors and intracellular signaling molecules [30]. By becoming associated with b-integrin receptors, which are translocated from granulocytic or vesicular stores to the plasma membrane upon cell stimulation vimentin and filamin A can facilitate the activation of local cellular processes [46].…”

Section: Discussionmentioning

confidence: 99%

“…3c) were identified as vimentin and filamin A. This indicates that during neutrophil activation these cytoskeletal proteins become tyrosylated possibly as a result of their being associated with the plasma membrane [30]. Spot 15 ( Fig.…”

Section: Identification Of Tyrosylated Proteins After Pma Activationmentioning

confidence: 91%

Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack. A proteomic study using a tyrosylating fluorophore

et al. 2004

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Tyrosyl radicals cross-linked to protein tyrosine residues (tyrosylated proteins) represent hallmarks of neutrophil-mediated injury at the inflammatory locus. Yet the proteins targeted by tyrosyl radicals in an intact cellular system remain to be elucidated. Here, we show that tyrosyl radicals generated by human neutrophils after activation by phorbol 12-myristate 13-acetate (PMA), interferon-g (IFN-g) or TNF-a could act in an autocrine manner by cross-linking to endogenous proteins. We have identified the tyrosylated proteins by using a membraneimpermeable tyrosine analogue, tyramine coupled to fluorescein (TyrFluo), in combination with proteomics techniques. Confocal microscopy images indicated that initially the tyrosylated proteins were localized in patches at the cell surface to become internalized subsequently. In the neutrophil membrane-associated proteome, lactoferrin was the prime target of tyrosylation. Out of three isoforms identified, an 80 kDa neutral isoform was tyrosylated more extensively than the 85 kD basic isoform, particularly after PMA activation. Although all three stimuli induced tyrosylation of the filamentous component vimentin, additional tyrosylated vimentin fragments were detected after IFN-g-and TNF-a-stimulation. Moreover, upon activation the bulk of vimentin behaved as a dimer (M r 120 kDa) being slightly tyrosylated, yet phosphorylated at Thr-425 possibly as a requirement for its externalization. Unexpectedly, bovine catalase added to end tyrosyl radicals formation was detected as a highly tyrosylated neutrophil-associated protein. A moderate stimulus-dependent tyrosylation of ATP synthaseb, a-enolase, glyceraldehyde 3-phosphate dehydrogenase, cytokeratin-10, filamin-A, and annexin-I was also observed. When the membrane-permeable probe (acetylTyrFluo) was used, protein tyrosylation was not observed indicating that the intracellular proteins were well protected against oxidative attack. This study shows that human neutrophils can modulate their proteome via a tyrosine oxidation pathway induced by pro-inflammatory mediators.

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“…The FLNs are found in animals, amoeba and at least one excavate, suggesting that FLNs arose early in evolutionary terms in ancestral eukaryotes that utilised an actin-based amoeboid motility mechanism (Fritz-Laylin et al 2010). The human genome contains three FLN genes, filamin A (FLNA), FLNB and FLNC (Stossel et al 2001). FLNA and FLNB are widely expressed , while FLNC expression is more restricted in cardiac and skeletal muscle (Maestrini et al 1993).…”

Section: Filamin Domain Organisation and Structurementioning

confidence: 99%

Filamin structure, function and mechanics: are altered filamin-mediated force responses associated with human disease?

Sutherland-Smith

2011

Biophys Rev

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The cytoskeleton framework is essential not only for cell structure and stability but also for dynamic processes such as cell migration, division and differentiation. The F-actin cytoskeleton is mechanically stabilised and regulated by various actin-binding proteins, one family of which are the filamins that cross-link F-actin into networks that greatly alter the elastic properties of the cytoskeleton. Filamins also interact with cell membraneassociated extracellular matrix receptors and intracellular signalling proteins providing a potential mechanism for cells to sense their external environment by linking these signalling systems. The stiffness of the external matrix to which cells are attached is an important environmental variable for cellular behaviour. In order for a cell to probe matrix stiffness, a mechanosensing mechanism functioning via alteration of protein structure and/or binding events in response to external tension is required. Current structural, mechanical, biochemical and human disease-associated evidence suggests filamins are good candidates for a role in mechanosensing.

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Filamins as integrators of cell mechanics and signalling

Cited by 903 publications

References 98 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

Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack. A proteomic study using a tyrosylating fluorophore

Filamin structure, function and mechanics: are altered filamin-mediated force responses associated with human disease?

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