Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

Mattila, Pieta K.; Batista, Facundo D.; Treanor, Bebhinn

doi:10.1083/jcb.201504137

Cited by 119 publications

(110 citation statements)

References 149 publications

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“…have made it possible to observe the detailed organization of actin filaments in B cells and begin to unravel the mechanisms by which cytoskeletal defects affect individual signalling pathways 9 . The emerging picture is that the cytoskeleton provides structural and energy-dependent regulation of biochemical reactions in the cell.…”

Section: Recent Advances In Cellular Imaging (Box 1) and Biophysical mentioning

confidence: 99%

“…Both in the absence and presence of antigen, BCR signalling operates in a continuous balance between kinase and phosphatase reactions. Pharmacological and genetic manipulations show that this balance is maintained by the cortical cytoskeleton 9 , suggesting that actin regulates the access of membrane kinases and phosphatases to their substrates. These effects can be explained by several distinct mechanisms involving the influence of cortical actin on the diffusion of membrane proteins 88 .…”

Section: [H1] Cytoskeletal Regulation Of Bcr Signallingmentioning

confidence: 99%

“…While initially designed for 2D imaging, 3D implementations are possible. Localization microscopy using TIRF illumination has been used to investigate the organization of the plasma membrane and the cortical cytoskeleton 9 .…”

Section: Structured Illumination Microscopy (Sim) This Technique Impmentioning

confidence: 99%

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Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

123

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The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton couples extensively to B cell receptor (BCR) signalling pathways and its defects can either enhance or suppress B cell activation. Recent insights from single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion, and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also play a role in the adaptation of B cell subsets to specialized tasks during antibody responses.3

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Section: Recent Advances In Cellular Imaging (Box 1) and Biophysical mentioning

confidence: 99%

Section: [H1] Cytoskeletal Regulation Of Bcr Signallingmentioning

confidence: 99%

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Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

123

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“…This organization is mediated by lipid-lipid, lipid-protein and proteinprotein interactions within the membrane (Simons and Gerl, 2010), and by membrane-cortical-cytoskeleton interactions (Jaqaman and Grinstein, 2012;Mattila et al, 2016;Morone et al, 2006). Much remains to be determined about the nature of nanoclustering, the mechanisms leading to it and its consequences for receptor signaling (Garcia-Parajo et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Ligand-induced growth and compaction of CD36 nanoclusters enriched in Fyn induces Fyn signaling

Githaka

Vega

Baird

et al. 2016

Journal of Cell Science

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Nanoclustering is an emerging organizational principle for membraneassociated proteins. The functional consequences of nanoclustering for receptor signaling remain largely unknown. Here, we applied quantitative multi-channel high-and super-resolution imaging to analyze the endothelial cell surface receptor CD36, the clustering of which upon binding to multivalent ligands, such as the anti-angiogenic factor thrombospondin-1 (TSP-1), is thought to be crucial for signaling. We found that a substantial fraction of unligated CD36 exists in nanoclusters, which not only promote TSP-1 binding but are also enriched with the downstream effector Fyn. Exposure to multivalent ligands (TSP-1 or anti-CD36 IgM) that result in larger and denser CD36 clusters activates Fyn. Conversely, pharmacological perturbations that prevent the enhancement of CD36 clustering by TSP-1 abrogate Fyn activation. In both cases, there is no detectable change in Fyn enrichment at CD36 nanoclusters. These observations reveal a crucial role for the basal organization of a receptor into nanoclusters that are enriched with the signal-transducing downstream effectors of that receptor, such that enhancement of clustering by multivalent ligands is necessary and sufficient to activate the downstream effector without the need for its de novo recruitment.

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“…Integrin signaling is a pathway that controls rearrangement of the actin cytoskeleton (24). It has been suggested that the actin cytoskeleton may regulate receptor signaling, which is particularly important for the B-cell receptor and dysregulated signaling may result in autoimmunity and malignancy (25).…”

Section: Discussionmentioning

confidence: 99%

Proteomic changes of CD4+/CD25+/forkhead box p3+ regulatory T cells in a 30‑day rat model of sepsis survival

2017

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Abstract. Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis. Studying the survivors of sepsis may explain the mechanisms of natural recovery. Therefore, a 30-day rat model of sepsis survival was established in the current study. Cluster of differentiation CD4 + /CD25 + /forkhead box p3 + Tregs were isolated from the blood and spleens of rats undergoing cecal ligation and puncture or sham surgery, using flow cytometry. Proteomic analysis was performed using nano high-performance liquid chromatography -mass spectrometry. Several different biological pathways associated with uncommon differentially-expressed proteins were identified in the blood and spleen survivor and sham groups. Extracellular-regulated kinase/mitogen-activated protein kinase, as well as integrin and actin cytoskeletal pathway elements, including Ras-related protein 1b, talin 1 and filamin A, were associated with Tregs in the blood. Pathway elements associated with cell cycle regulators in the B-cell translocation gene family of proteins, tumor necrosis factor receptor superfamily member 4, Hippo signaling, P70-S6 kinase 1, phosphatidylinositol 3-kinase/protein kinase B signaling and 1,25-dihydroxyvitamin D3 biosynthesis were associated with Tregs from the spleen including phosphatase 2A activator regulatory factor 4, histone arginine methyltransferase, CD4, major histocompatibility complex class I antigens, 14-3-3 protein θ and nicotinamide adenine dinucleotide phosphate cytochrome P450 reductase. These results explain the mechanism by which Tregs naturally recover and indicates that Tregs in the blood and spleen vary. Differentially-expressed proteins serving a role in these pathways provide additional insight for the identification of new targets for the diagnosis and treatment of sepsis.

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Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

Cited by 119 publications

References 149 publications

Cytoskeletal control of B cell responses to antigens

Cytoskeletal control of B cell responses to antigens

Ligand-induced growth and compaction of CD36 nanoclusters enriched in Fyn induces Fyn signaling

Proteomic changes of CD4+/CD25+/forkhead box p3+ regulatory T cells in a 30‑day rat model of sepsis survival

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