Annexin II Modulates Volume-activated Chloride Currents in Vascular Endothelial Cells

Nilius, Bernd; Gerke, Volker; Prenen, Jean; Szücs, G; Heinke, Stephan; Weber, Klaus; Droogmans, Guy

doi:10.1074/jbc.271.48.30631

Cited by 72 publications

(57 citation statements)

References 33 publications

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“…Perturbing the F-actin microfilament system with phalloidin or cytochalasin B did not interfere with the swelling-induced activation of VRACs in endothelial cells ). However, we have recently provided evidence that annexin II, a plasma membrane-associated, actin filament-binding protein plays a functional role in the activation of VRACs in CPAE cells, suggesting a role for the subplasma membrane cytoskeleton (Nilius et al 1996b). Whether the Rho-Rho kinase effects on VRACs are exerted via the subplasma membrane cytoskeleton remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…inhibitory effect of Y_27632, we repeatedly activated ICl,swell in the presence of the blocker. Repetitive stimulation of control CPAE cells with HTS activates ICl,swell without significant run-down (Nilius et al 1996b;see also Figs 2A and 4D). However, in the continuous presence of 10 ìÒ Y_27632, we observed a slow but substantial decay of current responses, which could not be attributed to a reduced cell swelling (Fig.…”

Section: Modulation Of Vracs By Y_27632 An Inhibitor Of Rho Kinasementioning

confidence: 99%

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Role of Rho and Rho kinase in the activation of volume‐regulated anion channels in bovine endothelial cells

Nilius

Voets

Prenen

et al. 1999

The Journal of Physiology

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130

104

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1. We have studied the modulation of volume-regulated anion channels (VRACs) by the small GTPase Rho and by one of its targets, Rho kinase, in calf pulmonary artery endothelial (CPAE) cells. 2. RT-PCR and immunoblot analysis showed that both RhoA and Rho kinase are expressed in CPAE cells. 3. ICl,swell, the chloride current through VRACs, was activated by challenging CPAE cells with a 25% hypotonic extracellular solution (HTS) or by intracellular perfusion with a pipette solution containing 100 ìÒ GTPãS. Pretreatment of CPAE cells with the Clostridium C2IN-C3 fusion toxin, which inactivatesRho by ADP ribosylation, significantly impaired the activation of ICl,swell in response to the HTS. The current density at +100 mV was 49 ± 13 pA pF¢ (n = 17) in pretreated cells compared with 172 ± 17 pA pF¢ (n = 21) in control cells. 5. The volume-independent activation of ICl,swell by intracellular perfusion with GTPãS was also impaired in C2IN-C3-pretreated cells (31 ± 7 pA pF¢, n = 11) compared with nontreated cells (132 ± 21 pA pF¢, n = 15). 6. Activation of ICl,swell was pertussis toxin (PTX) insensitive. 7. Y_27632, a blocker of Rho kinase, inhibited ICl,swell and delayed its activation. 8. Inhibition of Rho and of Rho kinase by the above-described treatments did not affect the extent of cell swelling in response to HTS. 9. These experiments provide strong evidence that the Rho-Rho kinase pathway is involved in the VRAC activation cascade.

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Section: Discussionmentioning

confidence: 99%

Section: Modulation Of Vracs By Y_27632 An Inhibitor Of Rho Kinasementioning

confidence: 99%

Role of Rho and Rho kinase in the activation of volume‐regulated anion channels in bovine endothelial cells

Nilius

Voets

Prenen

et al. 1999

The Journal of Physiology

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130

104

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“…For example, annexin IV inhibits calmodulin-sensitive Cl − channels (37,38) as well as Ca 2+ -activated Cl − channels (39). In endothelial cells the annexin II-S100A10 complex might be involved in regulation of the swelling-activated Cl − channel (40) and cystic fibrosis transmembrane conductance regulator (41).…”

Section: Discussionmentioning

confidence: 99%

Anoctamin 1 (Tmem16A) Ca ² ⁺ -activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin network

Pérez‐Cornejo

Gokhale

Duran

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

114

139

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The newly discovered Ca 2+ -activated Cl − channel (CaCC), Anoctamin 1 (Ano1 or TMEM16A), has been implicated in vital physiological functions including epithelial fluid secretion, gut motility, and smooth muscle tone. Overexpression of Ano1 in HEK cells or Xenopus oocytes is sufficient to generate Ca 2+ -activated Cl − currents, but the details of channel composition and the regulatory factors that control channel biology are incompletely understood. We used a highly sensitive quantitative SILAC proteomics approach to obtain insights into stoichiometric protein networks associated with the Ano1 channel. These studies provide a comprehensive footprint of putative Ano1 regulatory networks. We find that Ano1 associates with the signaling/scaffolding proteins ezrin, radixin, moesin, and RhoA, which link the plasma membrane to the cytoskeleton with very high stoichiometry. Ano1, ezrin, and moesin/radixin colocalize apically in salivary gland epithelial cells, and overexpression of moesin and Ano1 in HEK cells alters the subcellular localization of both proteins. Moreover, interfering RNA for moesin modifies Ano1 current without affecting its surface expression level. Another network associated with Ano1 includes the SNARE and SM proteins VAMP3, syntaxins 2 and -4, and syntaxin-binding proteins munc18b and munc18c, which are integral to translocation of vesicles to the plasma membrane. A number of other regulatory proteins, including GTPases, Ca 2+ -binding proteins, kinases, and lipid-interacting proteins are enriched in the Ano1 complex. These data provide stoichiometrically prioritized information about mechanisms regulating Ano1 function and trafficking to polarized domains of the plasma membrane.calcium | interactome | cross-linker | apical targeting

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“…These different forms seem to be present in distinct subcellular compartments; AnxA2 monomer is mainly cytosolic (49 -51), whereas the heterodimer has been described in the nucleus (52)(53)(54) and the heterotetramer is associated with the plasma membrane (55). The AnxA2 heterotetramer is the most abundant form of the protein, representing 90 -95% of the total AnxA2 in endothelial, epithelial, and Madin-Darby canine kidney cells (34,56). The p11 light chain regulates many of the activities of AnxA2 and confers to the heterotetramer biochemical properties distinct from those of the monomer (49,57,58).…”

Section: Discussionmentioning

confidence: 99%

New Insights into the tPA-Annexin A2 Interaction

Roda

Valero

Peiró

et al. 2003

Journal of Biological Chemistry

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Annexin A2 has been described as an important receptor for tissue-type plasminogen activator in endothelium and other cell types. Interaction between tissuetype plasminogen activator and its cellular receptor is critical for many of the functions of this protease. The annexin A2 motif that mediates tissue plasminogen activator interaction has been assigned to the hexapeptide LCKLSL in the amino-terminal domain of the protein, and it has been proposed that Cys 8 of this sequence is essential for tPA binding. In an attempt to identify other amino acids critical for tPA-annexin A2 interaction, we have analyzed a set of peptides containing several modifications of the original hexapeptide, including glycine scans, alanine scans, D-amino acid scans, conservative mutations, cysteine blocking, and enantiomer and retroenantiomer sequences. Using a non-radioactive competitive binding assay, we have found that all cysteinecontaining peptides, independently of their sequence, compete the interaction between tPA and annexin A2. Cysteine-containing peptides also inhibit tPA binding to the surface of cultured human umbilical vein endothelial cells (HUVEC). Mass spectrometry demonstrates that the peptides bind through a disulfide bond to a cysteine residue of annexin A2, the same mechanism that has been suggested for the inhibition mediated by homocysteine. These data call for a revision of the role of the LCKLSL sequence as the sole annexin A2 structural region required to bind tPA and indicate that further studies are necessary to better define the annexin A2-tPA interaction.

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Annexin II Modulates Volume-activated Chloride Currents in Vascular Endothelial Cells

Cited by 72 publications

References 33 publications

Role of Rho and Rho kinase in the activation of volume‐regulated anion channels in bovine endothelial cells

Role of Rho and Rho kinase in the activation of volume‐regulated anion channels in bovine endothelial cells

Anoctamin 1 (Tmem16A) Ca ² ⁺ -activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin network

New Insights into the tPA-Annexin A2 Interaction

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Annexin II Modulates Volume-activated Chloride Currents in Vascular Endothelial Cells

Cited by 72 publications

References 33 publications

Role of Rho and Rho kinase in the activation of volume‐regulated anion channels in bovine endothelial cells

Role of Rho and Rho kinase in the activation of volume‐regulated anion channels in bovine endothelial cells

Anoctamin 1 (Tmem16A) Ca 2 + -activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin network

New Insights into the tPA-Annexin A2 Interaction

Contact Info

Product

Resources

About

Anoctamin 1 (Tmem16A) Ca ² ⁺ -activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin network