Inside-Out Regulation of ICAM-1 Dynamics in TNF-α-Activated Endothelium

Buul, Jaap D. van; Rijssel, Jos van; Alphen, Floris P.J. van; Hoogenboezem, Mark; Tol, Simon; Hoeben, Kees A.; Marle, J. van; Mul, Frederik P. J.; Hordijk, Peter L.

doi:10.1371/journal.pone.0011336

Cited by 53 publications

(59 citation statements)

References 37 publications

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“…These include CD2AP (CMS) and caveolin-1 (Nethe et al, 2010;van Duijn et al, 2010) that also, like PACSIN2, regulate endocytosis (Lynch et al, 2003;Parton and Richards, 2003). However, whereas CD2AP is recruited to cell-cell contacts upon Rac1 activation, caveolin-1 translocates to FAs.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, PACSIN2 could block Rac1 regulation by GEF proteins. To investigate this, we performed pull-down experiments with the biotinylated Pak1-CRIB domain using cell lysates of HeLa cells that had been transfected with either TrioD1 or Tiam1-C1199, GEF proteins known to activate Rac1 (Habets et al, 1994;van Buul et al, 2010), and studied whether endogenous Rac1 activation still occurred in the presence of PACSIN2. PACSIN2-mediated downregulation of Rac1-GTP was found in the control situation, as well as in the presence of GEF proteins.…”

Section: Rac1-gtpmentioning

confidence: 99%

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The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration

Kreuk

Nethe

Fernandez‐Borja

et al. 2011

Journal of Cell Science

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The Rac1 GTPase controls cytoskeletal dynamics and is a key regulator of cell spreading and migration mediated by signaling through effector proteins, such as the PAK kinases and the Scar and WAVE proteins. We previously identified a series of regulatory proteins that associate with Rac1 through its hypervariable C-terminal domain, including the Rac1 activator β-Pix (also known as Rho guanine-nucleotide-exchange factor 7) and the membrane adapter caveolin-1. Here, we show that Rac1 associates, through its C-terminus, with the F-BAR domain protein PACSIN2, an inducer of membrane tubulation and a regulator of endocytosis. We show that Rac1 localizes with PACSIN2 at intracellular tubular structures and on early endosomes. Active Rac1 induces a loss of PACSIN2-positive tubular structures. By contrast, Rac1 inhibition results in an accumulation of PACSIN2-positive tubules. In addition, PACSIN2 appears to regulate Rac1 signaling; siRNA-mediated loss of PACSIN2 increases the levels of Rac1-GTP and promotes cell spreading and migration in a wound healing assay. Moreover, ectopic expression of PACSIN2 reduces Rac1-GTP levels in a fashion that is dependent on the PACSIN2–Rac1 interaction, on the membrane-tubulating capacity of PACSIN2 and on dynamin. These data identify the BAR-domain protein PACSIN2 as a Rac1 interactor that regulates Rac1-mediated cell spreading and migration.

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Section: Discussionmentioning

confidence: 99%

Section: Rac1-gtpmentioning

confidence: 99%

The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration

Kreuk

Nethe

Fernandez‐Borja

et al. 2011

Journal of Cell Science

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“…Inhibition of ROCK or myosin II significantly reduced the association of filamin B and a-actinin-4, but not that of cortactin, to ICAM-1 ( Importantly, the amount of clustered ICAM-1 that was isolated, as well as monolayer integrity was unaffected under any of these conditions (supplementary material Fig. S3D-G) (van Buul et al, 2010a). Taken together, these experiments show that ICAM-1 bound to the different actin-binding adaptor proteins is differentially regulated by F-actin (de)polymerization and contractility.…”

Section: Icam-1 Forms Molecularly Distinct Complexes With Adaptor Promentioning

confidence: 99%

Actin-binding proteins differentially regulate endothelial cell stiffness, ICAM-1 function and neutrophil transmigration

Schaefer

Riet

Ritz

et al. 2014

Journal of Cell Science

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Chronic vascular inflammation is driven by interactions between activated leukocytes and the endothelium. Leukocyte b2-integrins bind to endothelial intercellular adhesion molecule 1 (ICAM-1), which allows leukocyte spreading, crawling and transendothelial migration. Leukocytes scan the vascular endothelium for permissive sites to transmigrate, which suggests that there is apical membrane heterogeneity within the endothelium. However, the molecular basis for this heterogeneity is unknown. Leukocyte adhesion induces ICAM-1 clustering, which promotes its association to the actinbinding proteins filamin B, a-actinin-4 and cortactin. We show that these endothelial proteins differentially control adhesion, spreading and transmigration of neutrophils. Loss of filamin B, a-actinin-4 and cortactin revealed adaptor-specific effects on a nuclear-toperipheral gradient of endothelial cell stiffness. By contrast, increasing endothelial cell stiffness stimulates ICAM-1 function. We identify endothelial a-actinin-4 as a key regulator of endothelial cell stiffness and of ICAM-1-mediated neutrophil transmigration. Finally, we found that the endothelial lining of human and murine atherosclerotic plaques shows elevated levels of a-actinin-4. These results identify endothelial cell stiffness as an important regulator of endothelial surface heterogeneity and of ICAM-1 function, which in turn controls the adhesion and transmigration of neutrophils.

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“…Moreover, ICAM-1 is particularly enriched in F-actin-rich extensions called microvilli that protrude out of the EC apical surface (Fig. 3B) (24,37). Immunofluorescent analysis of annexin A2 and ICAM-1 showed enrichment of both proteins in microvilli (Fig.…”

Section: Icam-1 Is Localized In F-actin-and Annexin A2-rich Microvillimentioning

confidence: 94%

Annexin A2 Limits Neutrophil Transendothelial Migration by Organizing the Spatial Distribution of ICAM-1

Heemskerk

Asimuddin

Oort

et al. 2016

The Journal of Immunology

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ICAM-1 is required for firm adhesion of leukocytes to the endothelium. However, how the spatial organization of endothelial ICAM-1 regulates leukocyte adhesion is not well understood. In this study, we identified the calcium-effector protein annexin A2 as a novel binding partner for ICAM-1. ICAM-1 clustering promotes the ICAM-1–annexin A2 interaction and induces translocation of ICAM-1 into caveolin-1–rich membrane domains. Depletion of endothelial annexin A2 using RNA interference enhances ICAM-1 membrane mobility and prevents the translocation of ICAM-1 into caveolin-1–rich membrane domains. Surprisingly, this results in increased neutrophil adhesion and transendothelial migration under flow conditions and reduced crawling time, velocity, and lateral migration distance of neutrophils on the endothelium. In conclusion, our data show that annexin A2 limits neutrophil transendothelial migration by organizing the spatial distribution of ICAM-1.

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Inside-Out Regulation of ICAM-1 Dynamics in TNF-α-Activated Endothelium

Cited by 53 publications

References 37 publications

The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration

The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration

Actin-binding proteins differentially regulate endothelial cell stiffness, ICAM-1 function and neutrophil transmigration

Annexin A2 Limits Neutrophil Transendothelial Migration by Organizing the Spatial Distribution of ICAM-1

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