Roles of Rho GTPases in leucocyte and leukaemia cell transendothelial migration

Infante, Elvira; Ridley, Anne J.

doi:10.1098/rstb.2013.0013

Cited by 24 publications

(20 citation statements)

References 50 publications

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“…These observations are not in line with the current paradigm that RhoA is essential for front protrusion and back retraction of migrating cells. 45 Neutrophil migration in response to CXCL1, thioglycollate, zymosan particles, E coli, and IAV was strikingly augmented in the absence of Rho proteins, clearly indicating that Rho acts primarily as a negative regulator of migration in vivo. Common to all stimuli, usually restricted by Rho activity, is their b 2 integrin independence when triggering neutrophil influx.…”

Section: Discussionmentioning

confidence: 99%

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

Jennings¹,

Strengert²,

Hayes³

et al. 2014

Blood

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Section: Discussionmentioning

confidence: 99%

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

Jennings¹,

Strengert²,

Hayes³

et al. 2014

Blood

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“…7J). In vivo, the localizations of these proteins vary by cell type (5,9,88). Ezr is sometimes present at the leading edge in filopodia and lamellipodia in vivo, where it can play an important role in lamellipodia growth and stability.…”

Section: Figmentioning

confidence: 99%

“…The same was true for Diaph1 in silico (Figs. 7G and 7H) and in vivo (5,85). This node The cells displayed chemoattraction until they reached ϳ20 nM S1P, and then they displayed chemorepulsion.…”

Section: Fig 2 Protein Quantification Accuracy and Precision And Tmentioning

confidence: 99%

Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing

Manes

Angermann

Koppenol-Raab

et al. 2015

Molecular & Cellular Proteomics

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Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P) 1 regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq was used to identify expressed target proteins, and selected reaction monitoring (SRM) mass spectrometry using internal peptide standards was used to perform absolute abundance measurements of pathway proteins. The resulting transcript and protein abundance values were strongly correlated. Measured protein abundance values, used as simulation input parameters, led to in silico pathway behavior matching in vitro measurements. Moreover, once model parameters were established, even simulated responses toward stimuli that were not used for parameterization were consistent with experimental findings. These findings demonstrate the feasibility and value of combining targeted mass spectrometry with pathway modeling for advancing biological insight. Molecular & Cellular Proteomics 14: 10.1074/mcp.M115.048918, 2661-2681, 2015.Chemotaxis is defined as directed movement of a cell (or of an organism) resulting from stimulation by a chemokine or other chemotactic chemical. Eukaryotic cells employ intricate intracellular pathways to sense concentration differences of chemoattractants at their surface and move along such gradients using multiple synchronized cellular processes, including cell protrusion and adhesion at the leading end, de-adhesion at the trailing end, and mechanical force generation at both the leading and trailing ends (1-4).Activation of chemotactic receptors through chemoattractant concentration gradients results in nonuniform intracellular signaling responses that depend on numerous feedback mechanisms (5-7). Downstream, F-actin synthesis at the leading end causes the formation of cell protrusions (for example, filopodia, lamellipodia, and lamellae) that, in concert with actomyosin contraction, generates force at both the leading and trailing ends (8 -10). Chemotactic traction is produced by cell protrusions interacting with a confined environment and/or by adhesions that bind to the extracellular matrix and/or to cell adhesion molecules (11).Chemotaxis plays a major role in a wide range of physiological and pathophysiological processes. Sphingosine-1-phosphate (S1P), a phosphosphingolipid, mediates chemotaxis of many circulating cell types, including osteoclast precursors (OPs) (12)(13)(14). Osteoclasts are monocyte-derived multinuclear cells that directly attach to the bone matrix and resorb bone. They are solely responsible for bone resorption, and their misregulated activity has been imp...

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“…Impaired cytoskeletal dynamics and disarranged structural organization underlie several human diseases, including muscular dystrophy [24,25,26], cardiac disorders [27], liver diseases [28] and malignancies [29,30,31,32]. Since ChAc is a genetic disease affecting multiple organs including brain and blood, but also muscle and liver cells [4,7], disarranged cytoskeletal structures may not be limited to actin microfilaments.…”

Section: Introductionmentioning

confidence: 99%

Chorein Sensitive Arrangement of Cytoskeletal Architecture

Honisch

Hagen

et al. 2015

Cell Physiol Biochem

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Background/Aims: Chorein is a protein expressed in various cell types. Loss of function mutations of the chorein encoding gene VPS13A lead to chorea-acanthocytosis, an autosomal recessive genetic disease characterized by movement disorder and behavioral abnormalities. Recent observations revealed that chorein is a powerful regulator of actin cytoskeleton in erythrocytes, platelets, K562 and endothelial HUVEC cells. Methods: In the present study we have used Western blotting to study actin polymerization dynamics, laser scanning microscopy to evaluate in detail the role of chorein in microfilaments, microtubules and intermediate filaments cytoskeleton architecture and RT-PCR to assess gene transcription of the cytoskeletal proteins. Results: We report here powerful depolymerization of actin microfilaments both, in erythrocytes and fibroblasts isolated from chorea-acanthocytosis patients. Along those lines, morphological analysis of fibroblasts from chorea-acanthocytosis patients showed disarranged microtubular network, when compared to fibroblasts from healthy donors. Similarly, the intermediate filament networks of desmin and cytokeratins showed significantly disordered organization with clearly diminished staining in patient's fibroblasts. In line with this, RT-PCR analysis revealed significant downregulation of desmin and cytokeratin gene transcripts. Conclusion: Our results provide for the first time evidence that defective chorein is accompanied by significant structural disorganization of all cytoskeletal structures in human fibroblasts from chorea-acanthocytosis patients.

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Roles of Rho GTPases in leucocyte and leukaemia cell transendothelial migration

Cited by 24 publications

References 50 publications

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing

Chorein Sensitive Arrangement of Cytoskeletal Architecture

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