PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration

Janjanam, Jagadeesh; Chandaka, Giri K; Kotla, Sivareddy; Rao, Gadiparthi N.

doi:10.1091/mbc.e15-08-0570

Cited by 22 publications

(29 citation statements)

References 74 publications

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“…Overall, our data are supported by the recent findings of Janjanam and colleagues about the effects of MCP-1 in G-actin polymerization, F-actin stress fiber formation, and migration of human aortic SMCs41.…”

Section: Discussionsupporting

confidence: 91%

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Verzola

Milanesi

Bertolotto

et al. 2017

Sci Rep

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Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages. Mstn co-localized with α-smooth muscle actin (α-SMA) staining and with some CD45+ cells, indicating Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin, α-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs and monocyte biology and sustains a chronic inflammatory milieu. These findings propose to consider Mstn as a new playmaker in atherosclerosis progression.

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Section: Discussionsupporting

confidence: 91%

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Verzola

Milanesi

Bertolotto

et al. 2017

Sci Rep

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“…Reciprocally, β2AR-induced phosphorylation relied more on a PKA-dependent pathway. The data are consistent with the different signaling cascades ignited by the different GPCRs, CCR2 relying mainly on G i and G q which lead to PKC activation (Janjanam et al, 2015;Jiménez-Sainz et al, 2003), and β2AR on G s , leading to PKA activation. By contrast, it is well established that FLNa can be phosphorylated at S2152 by cAMP-dependent PKA Jay et al, 2004).…”

Section: Discussionsupporting

confidence: 75%

Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling

Pons

Izquierdo

Andreu-Carbó

et al. 2017

Journal of Cell Science

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Proper endosomal trafficking of ligand-activated G-protein-coupled receptors (GPCRs) is essential to spatiotemporally tune their physiological responses. For the monocyte chemoattractant receptor 2 (CCR2B; one of two isoforms encoded by CCR2), endocytic recycling is important to sustain monocyte migration, whereas filamin A (FLNa) is essential for CCL2-induced monocyte migration. Here, we analyze the role of FLNa in the trafficking of CCR2B along the endocytic pathway. In FLNa-knockdown cells, activated CCR2B accumulated in enlarged EEA-1-positive endosomes, which exhibited slow movement and fast fluorescence recovery, suggesting an imbalance between receptor entry and exit rates. Utilizing super-resolution microscopy, we observed that FLNa-GFP, CCR2B and β2-adrenergic receptor (β2AR) were present in actin-enriched endosomal microdomains. Depletion of FLNa decreased CCR2B association with these microdomains and concomitantly delayed CCR2B endosomal traffic, without apparently affecting the number of microdomains. Interestingly, CCR2B and β2AR signaling induced phosphorylation of FLNa at residue S2152, and this phosphorylation event was contributes to sustain receptor recycling. Thus, our data strongly suggest that CCR2B and β2AR signals to FLNa to stimulate its endocytosis and recycling to the plasma membrane.

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“…Because MCP-1 increased macrophage migration, 26 we determined whether the numbers of cells carrying individual podosomes or podosome rosettes were altered in response to MCP-1 and whether the knockout of KLF5 affected MCP-1-induced podosome formation. These experiments showed significantly greater numbers of macrophages containing podosome rosettes among MCP-1-treated cells than among untreated cells.…”

Section: Klf5 Deletion Reduces Podosome Rosette Formation In Macrophamentioning

confidence: 99%

Inhibition of KLF5–Myo9b–RhoA Pathway–Mediated Podosome Formation in Macrophages Ameliorates Abdominal Aortic Aneurysm

Zheng

Suzuki

et al. 2017

Circulation Research

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A bdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the remodeling of the aortic wall, and it frequently leads to high morbidity and mortality because of vascular dissection and rupture.1 Although AAA formation is a multifactorial process involving the infiltration of macrophages, release of proinflammatory cytokines and proteases, elastin breakdown, vascular smooth muscle cell (VSMC) apoptosis, and increased collagen turnover, macrophages are essential contributors to the pathogenesis of AAAs.2,3 Accordingly, monocytes/macrophages are reportedly activated by chronic inflammatory states, including atherosclerosis and oxidative stress, and by angiotensin II (Ang II) and inflammatory cytokines.Subsequently, macrophages infiltrate vessel walls, release proteases such as elastase, matrix metalloproteinase-12 (MMP-12) and metalloproteinases, and degrade extracellular matrix components such as collagen and elastin. 4,5 Simultaneously, infiltrating macrophages secrete inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interferon-γ, interleukin-1β, and interleukin-6, into the media and adventitia of aneurysmatic vessels, thereby, exacerbating inflammatory responses. 6Macrophage infiltration into vessel walls requires highly coordinated reorganization of actin cytoskeletal structures to create membrane protrusions called podosomes. 7 Human and murine podosomes contain many of the structural components

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PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration

Abstract: Phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in monocyte chemotactic protein 1–induced cytoskeleton remodeling, facilitating human aortic smooth muscle cell migration.

Cited by 22 publications

References 74 publications

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling

Inhibition of KLF5–Myo9b–RhoA Pathway–Mediated Podosome Formation in Macrophages Ameliorates Abdominal Aortic Aneurysm

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