Stimulation‐Dependent Recycling of Integrin β1 Regulated by ARF6 and Rab11

Powelka, Aimee M.; Sun, Jianlan; Li, Jian; Gao, Minggeng; Shaw, Leslie M.; Sonnenberg, Arnoud; Hsu, Victor

doi:10.1111/j.1600-0854.2004.00150.x

Cited by 311 publications

(398 citation statements)

References 75 publications

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“…b1 Integrin recycling was assessed by the decrease in internalized b1 integrin level resulted from its translocation from intracellular compartments to the plasma membrane. In the assay with iECs, b1 integrin inside the cell was detected by immunocytochemistry as previously reported 35,59 . In brief, iECs in cold PBS were incubated with an anti-b1 integrin antibody (1:200 dilution; HMb1-1, BioLegend) for 30 min on ice.…”

Section: Methodsmentioning

confidence: 97%

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Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling

et al. 2015

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Section: Methodsmentioning

confidence: 97%

“…Arf6 located at endosomes has been proposed to regulate serum-dependent recycling of b1 integrin 35,36 . However, HGF signalling has not been studied in this context.…”

Section: Endothelial Arf6 Regulates Tumour Angiogenesis and Growthmentioning

confidence: 99%

Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling

et al. 2015

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“…30 Other studies showed that trafficking of integrins in nucleated cells involves a Rab4-mediated fast route and a Rab11-mediated slow route. 22,24,35 Rab4 and Rab11 are both present in platelets, and their levels were unaffected by Arf6 deletion ( Figure 1A). Immunofluorescence analysis showed that Rab4 1 and Rab11 1 compartments were present but did not overlap, indicating that resting platelets contained both early and recycling endosomes ( Figure 6A).…”

mentioning

confidence: 99%

Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking

Huang¹,

Joshi²,

Xiang

et al. 2016

Blood

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• Arf6 selectively regulates endocytic trafficking of platelet a IIb b 3 .• Endocytosis contributes to acute platelet function.Platelet and megakaryocyte endocytosis is important for loading certain granule cargo (ie, fibrinogen [Fg] and vascular endothelial growth factor); however, the mechanisms of platelet endocytosis and its functional acute effects are understudied. Adenosine 5'-diphosphate-ribosylation factor 6 (Arf6) is a small guanosine triphosphate-binding protein that regulates endocytic trafficking, especially of integrins. To study platelet endocytosis, we generated platelet-specific Arf6 knockout (KO) mice. Arf6 KO platelets had less associated Fg suggesting that Arf6 affects a IIb b 3 -mediated Fg uptake and/or storage. Other cargo was unaffected. To measure Fg uptake, mice were injected with biotinylated-or fluorescein isothiocyanate (FITC)-labeled Fg. Platelets from the injected Arf6 KO mice showed lower accumulation of tagged Fg, suggesting an uptake defect. Ex vivo, Arf6 KO platelets were also defective in FITC-Fg uptake and storage. Immunofluorescence analysis showed initial trafficking of FITC-Fg to a Rab4-positive compartment followed by colocalization with Rab11-positive structures, suggesting that platelets contain and use both early and recycling endosomes. Resting and activated a IIb b 3 levels, as measured by flow cytometry, were unchanged; yet, Arf6 KO platelets exhibited enhanced spreading on Fg and faster clot retraction. This was not the result of alterations in a IIb b 3 signaling, because myosin light-chain phosphorylation and Rac1/RhoA activation were unaffected. Consistent with the enhanced clot retraction and spreading, Arf6 KO mice showed no deficits in tail bleeding or FeCl 3 -induced carotid injury assays. Our studies present the first mouse model for defining the functions of platelet endocytosis and suggest that altered integrin trafficking may affect the efficacy of platelet function. (Blood. 2016;127(11):1459-1467 IntroductionIt is increasingly clear that platelets are capable of different types of intracellular membrane trafficking. Platelet exocytosis and autophagy are critical for hemostasis. [1][2][3][4] Platelet endocytosis is important for granule cargo loading. Platelets selectively take up certain cargo (ie, fibrinogen [Fg] and vascular endothelial growth factor) from plasma and package it into a-granules. [5][6][7][8] However, the molecular mechanisms of platelet endocytosis are largely unknown. It is also unclear whether platelet endocytosis contributes to acute platelet functions beyond granule cargo loading. The goal of this study is to begin to address these fundamental questions.The Ras-like, small guanosine triphosphate (GTP)-binding proteins called adenosine 5'-diphosphate-ribosylation factors (Arf's), are key intracellular trafficking regulators. They cycle between inactive guanosine diphosphate (GDP)-bound and active GTP-bound states and are important for multiple functions (eg, actin cytoskeleton remodeling, lipid metabolism, and vesicle traffickin...

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“…Moreover, RCP/Rab11-driven recycling of ␣5␤1-integrin controls the activation of Rac and RhoA in different cell lines (A2780, MDA-MB-231 and HT1080 cells) (Jacquemet et al, 2013). The recycling of ␤1-integrin is known to be regulated by Arf6 and Rab11 (Eva et al, 2010(Eva et al, , 2012Powelka et al, 2004) and Rab11 was also implied in the targeted delivery of Src tyrosine kinases to FAs (Bach et al, 2014) where Src contributes to the phosphorylation of FAK (Canel et al, 2013). In addition, ␤1-integrin recruitment can lead to an activation of Rac1 in HeLa cells (O'Toole et al, 2011).…”

Section: Influence Of Reggie On Fak Rac1 and Rab11 Activationmentioning

confidence: 99%

Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover via Rab11a

Hülsbusch

Solis

Katanaev

et al. 2015

European Journal of Cell Biology

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a b s t r a c tReggies/flotillins are implicated in trafficking of membrane proteins to their target sites and in the regulation of the Rab11a-dependent targeted recycling of E-cadherin to adherens junctions (AJs). Here we demonstrate a function of reggies in focal adhesion (FA) formation and ␣5-and ␤1-integrin recycling to FAs. Downregulation of reggie-1 in HeLa and A431 cells by siRNA and shRNA increased the number of FAs, impaired their distribution and modified FA turnover. This was coupled to enhanced focal adhesion kinase (FAK) and Rac1 signaling and gain in plasma membrane motility. Wild type and constitutively-active (CA) Rab11a rescued the phenotype (normal number of FAs) whereas dominant-negative (DN) Rab11a mimicked the loss-of-reggie phenotype in control cells. That reggie-1 affects integrin trafficking emerged from the faster loss of internalized antibody-labeled ␤1-integrin in reggie-deficient cells. Moreover, live imaging using TIRF microscopy revealed vesicles containing reggie-1 and ␣5-or ␤1-integrin, trafficking close to the substrate-near membrane and making kiss-and-run contacts with FAs. Thus, reggie-1 in interaction with Rab11a controls Rac1 and FAK activation and coordinates the targeted recycling of ␣5-and ␤1-integrins to FAs to regulate FA formation and membrane dynamics.

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Stimulation‐Dependent Recycling of Integrin β1 Regulated by ARF6 and Rab11

Cited by 311 publications

References 75 publications

Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling

Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling

Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking

Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover via Rab11a

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