ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons

Eva, Richard; Crisp, Sarah; Marland, Jamie R. K.; Norman, Jim C.; Kanamarlapudi, Venkateswarlu; ffrench‐Constant, Charles; Fawcett, James W.

doi:10.1523/jneurosci.1409-12.2012

Cited by 88 publications

(102 citation statements)

References 74 publications

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“…The Rab11/ARF-6 dependent recycling of integrins was demonstrated by Eva and colleagues as an essential molecular mechanism for the regeneration of axons in mammals (Eva et al, 2010(Eva et al, , 2012. This is in line with our present results on the interaction of reggie and Rab11a at trafficking cargo vesicles during cell migration (Stuermer, 2010).…”

Section: Conserved Role Of Reggie In Targeted Delivery Of Cargo?supporting

confidence: 93%

“…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%

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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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Section: Conserved Role Of Reggie In Targeted Delivery Of Cargo?supporting

confidence: 93%

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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“…IQSEC1(mRNA) and subsequent Arf6 (protein) are highly expressed in the brain [65]. This molecule is involved in actin dynamics, lipid modification and membrane trafficking, specifically axonal transport after damage [66,67].…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Jadavji

Farr

Lips

et al. 2015

Behavioural Brain Research

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(2015) Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. Behavioural Brain Research, 283 . pp. 215-226. ISSN 1872-7549 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/32983/9/UNG_FADD_20140826_manuscript_final.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. ABSTRACTDietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders.Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfusion in an animal model. Ung+/+ and Ung−/− mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung−/− FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung+/+ FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung−/− hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion o...

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“…7,17,18 Although unknown in platelets, Arf6 clearly affects integrin trafficking in other cells: both endocytosis and recycling. [19][20][21] In cancer cells, active and inactive b 1 integrins traffic via different endocytic recycling routes, although their endocytosis equally requires both clathrin and dynamin. 22 Integrins can be recycled back to the plasma membrane, either via a Rab4-mediated short loop, recycling from early endosomes, or via a Rab11-mediated long loop, recycling from a perinuclear The online version of this article contains a data supplement.…”

Section: Introductionmentioning

confidence: 99%

“…32 Alternatively, in neurons, Arf6 inactivation increases recycling of a 9 b 1 through a Rab4-mediated pathway and increases axonal growth. 19 To investigate roles for Arf6 in a IIb b 3 -mediated spreading, we performed time-course studies of platelet spreading on Fg-coated surfaces. Surprisingly, Arf6 KO platelets spread faster compared with WT without affecting initial static adhesion (Figure 4).…”

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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ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons

Cited by 88 publications

References 74 publications

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

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

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking

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