Membrane microviscosity regulates endothelial cell motility

Ghosh, Pradip; Vasanji, Amit; Murugesan, Gurunathan; Eppell, Steven J.; Graham, Linda M.; Fox, Paul L.

doi:10.1038/ncb873

Cited by 79 publications

(79 citation statements)

References 30 publications

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“…These values are in line with the K d values obtained for bFGF and VEGF binding to their respective receptors (Neufeld and Gospodarowicz, 1985;Soker et al, 1996). By comparison, in previous studies using these growth factors, concentrations between 1 and 10 ng/ml were used to measure the effects of VEGF and bFGF on the migration of cultured ECs (Yoshida et al, 1996;Ghosh et al, 2002).…”

Section: Discussionsupporting

confidence: 49%

Nerve Growth Factor-Induced Migration of Endothelial Cells

Dollé¹,

Rezvan²,

Allen³

et al. 2005

J Pharmacol Exp Ther

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Nerve growth factor (NGF) is a well known neurotropic and neurotrophic agonist in the nervous system, which recently was shown to also induce angiogenic effects in endothelial cells (ECs). To measure NGF effects on the migration of cultured ECs, an important step in neoangiogenesis, we optimized an omnidirectional migration assay using human aortic endothelial cells (HAECs) and validated the assay with human recombinant basic fibroblast growth factor (rhbFGF) and human recombinant vascular endothelial growth factor (rhVEGF). The potencies of nerve growth factor purified from various species (viper, mouse, and recombinant human) to stimulate HAEC migration was similar to that of VEGF and basic fibroblast growth factor (bFGF) (EC 50 of ϳ0.5 ng/ml). Recombinant human bFGF was significantly more efficacious than either viper NGF or rhVEGF, both of which stimulated HAEC migration by ϳ30% over basal spontaneous migration. NGF-mediated stimulation of HAEC migration was completely blocked by the NGF/TrkA receptor antagonist K252a [(8R*,9S*,11S*)-(ı)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,-8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(c,d,e)trindene-1-one] (30 nM) but not by the VEGF/Flk receptor antagonist ) methylidenyl]-indolin-2-one] (250 nM), indicating a direct effect of NGF via TrkA receptor activation on HAEC migration. Viper NGF stimulation of HAEC migration was additively increased by either rhVEGF or rhbFGF, suggesting a potentiating interaction between their tyrosine kinase receptor signaling pathways. Viper NGF represents a novel pharmacological tool to investigate possible TrkA receptor subtypes in endothelial cells. The ability of NGF to stimulate migration of HAEC cells in vitro implies that this factor may play an important role in the cardiovascular system besides its well known effects in the nervous system.

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Section: Discussionsupporting

confidence: 49%

Nerve Growth Factor-Induced Migration of Endothelial Cells

Dollé¹,

Rezvan²,

Allen³

et al. 2005

J Pharmacol Exp Ther

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“…Down-regulation of TRPC6 inhibits TRPC5 activation, suggesting a TRPC6-dependent activation of TRPC5 by lysoPC. Although increased [Ca 2ϩ ] i is only one of several pathways by which lysoPC inhibits EC migration (Ghosh et al, 2002;Chaudhuri et al, 2005), partial preservation of migration is achieved by preventing the lysoPC-induced [Ca 2ϩ ] i rise. A better understanding of the TRPC6-TRPC5 activation cascade will allow development of therapeutic agents to preserve EC movement and promote angiogenesis and healing of EC injuries in atherosclerotic arteries.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of a TRPC6-TRPC5 Channel Cascade That Restricts Endothelial Cell Movement

Chaudhuri

Colles²,

Wagoner³

et al. 2008

MBoC

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“…To investigate whether alterations in the mobility of membrane microdomain components could be mechanistically linked to integrin-mediated uptake of bacteria, we treated cells with Tween20, a detergent that has been shown to enhance the mobility of membrane proteins (Ghosh et al, 2002;Sergent et al, 2005). Tween20 did not affect bacterial adhesion, but strongly increased the number of internalized bacteria (Fig.…”

Section: Enhanced Bacterial Uptake By Cav1 -/-Cells Is Not Due To Modmentioning

confidence: 99%

Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens

Hoffmann

Berking

Agerer

et al. 2010

Journal of Cell Science

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SummaryStaphylococcus aureus, which is a leading cause of hospital-acquired infections, binds via fibronectin to integrin 51, a process that can promote host colonization in vivo. Integrin engagement induces actin cytoskeleton rearrangements that result in the uptake of S. aureus by non-professional phagocytic cells. Interestingly, we found that fibronectin-binding S. aureus trigger the redistribution of membrane microdomain components. In particular, ganglioside GM1 and GPI-linked proteins were recruited upon integrin 1 engagement, and disruption of membrane microdomains blocked bacterial internalization. Several membrane-microdomain-associated proteins, such as flotillin-1 and flotillin-2, as well as caveolin, were recruited to sites of bacterial attachment. Whereas dominantnegative versions of flotillin-2 did not affect bacterial attachment or internalization, cells deficient for caveolin-1 (Cav1 -/-) showed increased uptake of S. aureus and other Fn-binding pathogens. Recruitment of membrane microdomains to cell-associated bacteria was unaltered in Cav1 -/-cells. However, fluorescence recovery after photobleaching (FRAP) revealed an enhanced mobility of membranemicrodomain-associated proteins in the absence of caveolin-1. Enhanced membrane microdomain mobility and increased uptake of S. aureus was repressed by expression of wild-type caveolin-1, but not caveolin-1 G83S, which harbors a point mutation in the caveolin scaffolding domain. Similarly, chemical or physical stimulation of membrane fluidity led to increased uptake of S. aureus. These results highlight a crucial role for caveolin-1 in negative regulation of membrane microdomain mobility, thereby affecting endocytosis of bacteria-engaged integrins. This process might not only limit host cell invasion by integrin-binding bacterial pathogens, but might also be physiologically relevant for integrin-mediated cell adhesion.

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Membrane microviscosity regulates endothelial cell motility

Cited by 79 publications

References 30 publications

Nerve Growth Factor-Induced Migration of Endothelial Cells

Nerve Growth Factor-Induced Migration of Endothelial Cells

Elucidation of a TRPC6-TRPC5 Channel Cascade That Restricts Endothelial Cell Movement

Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens

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