Search results for "focal adhesions"

Bifunctional Hydrogels Containing the Laminin Motif IKVAV Promote Neurogenesis

2017

Summary Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adh…

Variation in genomic landscape of clear cell renal cell carcinoma across Europe

2014

The incidence of renal cell carcinoma (RCC) is increasing worldwide, and its prevalence is particularly high in some parts of Central Europe. Here we undertake whole-genome and transcriptome sequencing of clear cell RCC (ccRCC), the most common form of the disease, in patients from four different European countries with contrasting disease incidence to explore the underlying genomic architecture of RCC. Our findings support previous reports on frequent aberrations in the epigenetic machinery and PI3K/mTOR signalling, and uncover novel pathways and genes affected by recurrent mutations and abnormal transcriptome patterns including focal adhesion, components of extracellular matrix (ECM) and …

Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway

2012

A novel virus- and integrin clustering–specific pathway diverts integrin from its normal endo/exocytic traffic to a nonrecycling degradative endosomal route. Clustering of α2β1 integrin causes redistribution of the integrin to perinuclear endosomes, leading to enhanced integrin turnover promoted by calpains.

α-parvin is required for epidermal morphogenesis, hair follicle development and basal keratinocyte polarity

2020

Epidermal morphogenesis and hair follicle (HF) development depend on the ability of keratinocytes to adhere to the basement membrane (BM) and migrate along the extracellular matrix. Integrins are cell-matrix receptors that control keratinocyte adhesion and migration, and are recognized as major regulators of epidermal homeostasis. How integrins regulate the behavior of keratinocytes during epidermal morphogenesis remains insufficiently understood. Here, we show that alpha-parvin (alpha-pv), a focal adhesion protein that couples integrins to actin cytoskeleton, is indispensable for epidermal morphogenesis and HF development. Inactivation of the murine alpha-pv gene in basal keratinocytes res…

Differentiative pathway activated by 3-aminobenzamide in human osteosarcoma MG-63 cells involves FAK and PAK activities.

2006

Integrative genomic and proteomic analyses identify targets for Lkb1 deficient metastatic lung tumors

2010

SummaryIn mice, Lkb1 deletion and activation of KrasG12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathw…

Focal adhesions are hotspots for keratin filament precursor formation

2006

Recent studies showed that keratin filament (KF) formation originates primarily from sites close to the actin-rich cell cortex. To further characterize these sites, we performed multicolor fluorescence imaging of living cells and found drastically increased KF assembly in regions of elevated actin turnover, i.e., in lamellipodia. Abundant KF precursors (KFPs) appeared within these areas at the distal tips of actin stress fibers, moving alongside the stress fibers until their integration into the peripheral KF network. The earliest KFPs were detected next to actin-anchoring focal adhesions (FAs) and were only seen after the establishment of FAs in emerging lamellipodia. Tight spatiotemporal …

A DNA‐Encoded FRET Biosensor for Visualizing the Tension across Paxillin in Living Cells upon Shear Stress

2022

Paxillin is a potential participant in the direct intracellular force transmission which is considered as the foundation of cells sensing and responding to extracellular environment. However, the detection of tension across paxillin has not been achieved due to lacking microsized tools. Herein, a paxillin tension sensor (PaxTs) based on Fluorescence Resonance Energy Transfer (FRET) technique was constructed. PaxTs can be expressed and assembled to FA sites spontaneously to visualize the tension across paxillin with FRET efficiency of ~62.4% in living cells. The tension across paxillin was found to decrease upon shear stress, in which the membrane fluidity and contractility of actin acted as…