scholarly journals Into the breach: how cells cope with wounds

Open Biology ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 180135 ◽  
Author(s):  
Mitsutoshi Nakamura ◽  
Andrew N. M. Dominguez ◽  
Jacob R. Decker ◽  
Alexander J. Hull ◽  
Jeffrey M. Verboon ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Repair Process ◽  
Molecular Techniques ◽  
Membrane Cytoskeleton ◽  
Type Size ◽  
Cortical Cytoskeleton ◽  
Repair Models

Repair of wounds to individual cells is crucial for organisms to survive daily physiological or environmental stresses, as well as pathogen assaults, which disrupt the plasma membrane. Sensing wounds, resealing membranes, closing wounds and remodelling plasma membrane/cortical cytoskeleton are four major steps that are essential to return cells to their pre-wounded states. This process relies on dynamic changes of the membrane/cytoskeleton that are indispensable for carrying out the repairs within tens of minutes. Studies from different cell wound repair models over the last two decades have revealed that the molecular mechanisms of single cell wound repair are very diverse and dependent on wound type, size, and/or species. Interestingly, different repair models have been shown to use similar proteins to achieve the same end result, albeit sometimes by distinctive mechanisms. Recent studies using cutting edge microscopy and molecular techniques are shedding new light on the molecular mechanisms during cellular wound repair. Here, we describe what is currently known about the mechanisms underlying this repair process. In addition, we discuss how the study of cellular wound repair—a powerful and inducible model—can contribute to our understanding of other fundamental biological processes such as cytokinesis, cell migration, cancer metastasis and human diseases.

scholarly journals Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling

2011 ◽  
Vol 193 (3) ◽  
pp. 455-464 ◽  
Author(s):  
Maria Teresa Abreu-Blanco ◽  
Jeffrey M. Verboon ◽  
Susan M. Parkhurst
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Single Cell ◽  
Wound Repair ◽  
Single Cells ◽  
Repair Process ◽  
Wound Edge ◽  
Cytoskeletal Remodeling ◽  
Tissue Integrity ◽  
E Cadherin

When single cells or tissues are injured, the wound must be repaired quickly in order to prevent cell death, loss of tissue integrity, and invasion by microorganisms. We describe Drosophila as a genetically tractable model to dissect the mechanisms of single-cell wound repair. By analyzing the expression and the effects of perturbations of actin, myosin, microtubules, E-cadherin, and the plasma membrane, we define three distinct phases in the repair process—expansion, contraction, and closure—and identify specific components required during each phase. Specifically, plasma membrane mobilization and assembly of a contractile actomyosin ring are required for this process. In addition, E-cadherin accumulates at the wound edge, and wound expansion is excessive in E-cadherin mutants, suggesting a role for E-cadherin in anchoring the actomyosin ring to the plasma membrane. Our results show that single-cell wound repair requires specific spatial and temporal cytoskeleton responses with distinct components and mechanisms required at different stages of the process.

Mechanism of protein sorting during erythroblast enucleation: role of cytoskeletal connectivity

Blood ◽  
2004 ◽  
Vol 103 (5) ◽  
pp. 1912-1919 ◽  
Author(s):  
James C.-M. Lee ◽  
J. Aura Gimm ◽  
Annie J. Lo ◽  
Mark J. Koury ◽  
Sharon W. Krauss ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Immunofluorescence Microscopy ◽  
Protein Sorting ◽  
Membrane Cytoskeleton ◽  
Skeletal Protein ◽  
Regulate Protein ◽  
Membrane Components ◽  
Cytoskeletal Elements

AbstractDuring erythroblast enucleation, nuclei surrounded by plasma membrane separate from erythroblast cytoplasm. A key aspect of this process is sorting of erythroblast plasma membrane components to reticulocytes and expelled nuclei. Although it is known that cytoskeletal elements actin and spectrin partition to reticulocytes, little is understood about molecular mechanisms governing plasma membrane protein sorting. We chose glycophorin A (GPA) as a model integral protein to begin investigating protein-sorting mechanisms. Using immunofluorescence microscopy and Western blotting we found that GPA sorted predominantly to reticulocytes. We hypothesized that the degree of skeletal linkage might control the sorting pattern of transmembrane proteins. To explore this hypothesis, we quantified the extent of GPA association to the cytoskeleton in erythroblasts, young reticulocytes, and mature erythrocytes using fluorescence imaged microdeformation (FIMD) and observed that GPA underwent dramatic reorganization during terminal differentiation. We discovered that GPA was more connected to the membrane cytoskeleton, either directly or indirectly, in erythroblasts and young reticulocytes than in mature cells. We conclude that skeletal protein association can regulate protein sorting during enucleation. Further, we suggest that the enhanced rigidity of reticulocyte membranes observed in earlier investigations results, at least in part, from increased connectivity of GPA with the spectrin-based skeleton.

scholarly journals β-arrestin mediates communication between plasma membrane and intracellular GPCRs to regulate signaling

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Maxwell S. DeNies ◽  
Alan V. Smrcka ◽  
Santiago Schnell ◽  
Allen P. Liu
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Cxc Chemokine Receptor 4 ◽  
Gpcr Activation ◽  
Cxc Chemokine ◽  
Cationic Channel ◽  
Highly Correlated ◽  
Chemokine Receptor 4 ◽  
G Protein Coupled

AbstractIt has become increasingly apparent that G protein-coupled receptor (GPCR) localization is a master regulator of cell signaling. However, the molecular mechanisms involved in this process are not well understood. To date, observations of intracellular GPCR activation can be organized into two categories: a dependence on OCT3 cationic channel-permeable ligands or the necessity of endocytic trafficking. Using CXC chemokine receptor 4 (CXCR4) as a model, we identified a third mechanism of intracellular GPCR signaling. We show that independent of membrane permeable ligands and endocytosis, upon stimulation, plasma membrane and internal pools of CXCR4 are post-translationally modified and collectively regulate EGR1 transcription. We found that β-arrestin-1 (arrestin 2) is necessary to mediate communication between plasma membrane and internal pools of CXCR4. Notably, these observations may explain that while CXCR4 overexpression is highly correlated with cancer metastasis and mortality, plasma membrane localization is not. Together these data support a model where a small initial pool of plasma membrane-localized GPCRs are capable of activating internal receptor-dependent signaling events.

scholarly journals β-arrestin mediates communication between plasma membrane and intracellular GPCRs to regulate signaling

2020 ◽  
Author(s):  
Maxwell S. DeNies ◽  
Alan Smrcka ◽  
Santiago Schnell ◽  
Allen P. Liu
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Cxc Chemokine Receptor 4 ◽  
Gpcr Activation ◽  
Cxc Chemokine ◽  
Cationic Channel ◽  
Highly Correlated ◽  
Chemokine Receptor 4 ◽  
G Protein Coupled

AbstractIt has become increasingly apparent that G protein-coupled receptor (GPCR) localization is a master regulator of cell signaling. However, the molecular mechanisms involved in this process are not well understood. To date, observations of intracellular GPCR activation can be organized into two categories: a dependence on OCT3 cationic channel-permeable ligands or the necessity of endocytic trafficking. Using CXC chemokine receptor 4 (CXCR4) as a model, we identified a third mechanism of intracellular GPCR signaling. We show that independent of membrane permeable ligands and endocytosis, upon stimulation, plasma membrane and internal pools of CXCR4 are post-translationally modified and collectively regulate EGR1 transcription. We found that β-arrestin-1 (arrestin 2) is necessary to mediate communication between plasma membrane and internal pools of CXCR4. Notably, these observations may explain that while CXCR4 overexpression is highly correlated with cancer metastasis and mortality, plasma membrane localization is not. Together these data support a model were a small initial pool of plasma membrane-localized GPCRs are capable of activating internal receptor-dependent signaling events.

scholarly journals Loss of the F-BAR protein CIP4 reduces platelet production by impairing membrane-cytoskeleton remodeling

Blood ◽  
2013 ◽  
Vol 122 (10) ◽  
pp. 1695-1706 ◽  
Author(s):  
Yolande Chen ◽  
Jorie Aardema ◽  
Sayali Kale ◽  
Zakary L. Whichard ◽  
Arinola Awomolo ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Platelet Production ◽  
Cortical Tension ◽  
Membrane Cytoskeleton ◽  
Key Points ◽  
Membrane Reorganization ◽  
Cytoskeleton Remodeling ◽  
Cortical Cytoskeleton

Key Points CIP4 affects the remodeling of both plasma membrane and cortical cytoskeleton in megakaryocytes. CIP4 in platelet biogenesis involves cortical tension, as does WASP, and WASP-independent plasma membrane reorganization.

scholarly journals Autocrine insulin pathway signaling regulates actin dynamics in cell wound repair

PLoS Genetics ◽  
2020 ◽  
Vol 16 (12) ◽  
pp. e1009186
Author(s):  
Mitsutoshi Nakamura ◽  
Jeffrey M. Verboon ◽  
Tessa E. Allen ◽  
Maria Teresa Abreu-Blanco ◽  
Raymond Liu ◽  
...  
Keyword(s):  
Wound Repair ◽  
Molecular Mechanisms ◽  
Actin Dynamics ◽  
Cell Cortex ◽  
Healthy Individuals ◽  
Actin Remodeling ◽  
Ring Assembly ◽  
Drug Inhibition ◽  
Inhibition Studies ◽  
Cortical Cytoskeleton

Cells are exposed to frequent mechanical and/or chemical stressors that can compromise the integrity of the plasma membrane and underlying cortical cytoskeleton. The molecular mechanisms driving the immediate repair response launched to restore the cell cortex and circumvent cell death are largely unknown. Using microarrays and drug-inhibition studies to assess gene expression, we find that initiation of cell wound repair in the Drosophila model is dependent on translation, whereas transcription is required for subsequent steps. We identified 253 genes whose expression is up-regulated (80) or down-regulated (173) in response to laser wounding. A subset of these genes were validated using RNAi knockdowns and exhibit aberrant actomyosin ring assembly and/or actin remodeling defects. Strikingly, we find that the canonical insulin signaling pathway controls actin dynamics through the actin regulators Girdin and Chickadee (profilin), and its disruption leads to abnormal wound repair. Our results provide new insight for understanding how cell wound repair proceeds in healthy individuals and those with diseases involving wound healing deficiencies.

scholarly journals From wound response to repair – lessons from C. elegans

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yicong Ma ◽  
Jing Xie ◽  
Chandra Sugiarto Wijaya ◽  
Suhong Xu
Keyword(s):  
Wound Repair ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Repair Process ◽  
Tissue Level ◽  
Wound Response ◽  
Membrane Repair ◽  
General Process ◽  
C Elegans

AbstractAs a result of evolution, the ability to repair wounds allows organisms to combat environment insults. Although the general process of wound healing at the tissue level has been described for decades, the detailed molecular mechanisms regarding the early wound response and rapid wound repair at the cellular level remain little understood. Caenorhabditis elegans is a model organism widely used in the field of development, neuroscience, programmed cell death etc. The nematode skin is composed of a large epidermis associated with a transparent extracellular cuticle, which likely has a robust capacity for epidermal repair. Yet, until the last decades, relatively few studies had directly analyzed the wound response and repair process. Here we review recent findings in how C. elegans epidermis responds to wounding and initiates early actin-polymerization-based wound closure as well as later membrane repair. We also discussed some remained outstanding questions for future study.

scholarly journals Autocrine insulin pathway signaling regulates actin dynamics in cell wound repair

2020 ◽  
Author(s):  
Mitsutoshi Nakamura ◽  
Jeffrey M. Verboon ◽  
Tessa E. Allen ◽  
Maria Teresa Abreu-Blanco ◽  
Raymond Liu ◽  
...  
Keyword(s):  
Wound Repair ◽  
Molecular Mechanisms ◽  
Actin Dynamics ◽  
Cell Cortex ◽  
Healthy Individuals ◽  
Actin Remodeling ◽  
Ring Assembly ◽  
Drug Inhibition ◽  
Inhibition Studies ◽  
Cortical Cytoskeleton

AbstractCells are exposed to frequent mechanical and/or chemical stressors that can compromise the integrity of the plasma membrane and underlying cortical cytoskeleton. The molecular mechanisms driving the immediate repair response launched to restore the cell cortex and circumvent cell death are largely unknown. Using microarrays and drug-inhibition studies to assess gene expression, we find that initiation of cell wound repair in the Drosophila model is dependent on translation, whereas transcription is required for subsequent steps. We identified 253 genes whose expression is up-regulated (80) or down-regulated (173) in response to laser wounding. A subset of these genes were validated using RNAi knockdowns and exhibit aberrant actomyosin ring assembly and/or actin remodeling defects. Strikingly, we find that the canonical insulin signaling pathway controls actin dynamics through the actin regulators Girdin and Chickadee (profilin), and its disruption leads to abnormal wound repair. Our results provide new insight for understanding how cell wound repair proceeds in healthy individuals and those with diseases involving wound healing deficiencies.

scholarly journals Revising Endosomal Trafficking under Insulin Receptor Activation

2021 ◽  
Vol 22 (13) ◽  
pp. 6978
Author(s):  
Maria J. Iraburu ◽  
Tommy Garner ◽  
Cristina Montiel-Duarte
Keyword(s):  
Plasma Membrane ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
Small Gtpases ◽  
Early Endosome ◽  
Tyrosine Kinase Receptors ◽  
Endosomal Trafficking ◽  
Cell Functions

The endocytosis of ligand-bound receptors and their eventual recycling to the plasma membrane (PM) are processes that have an influence on signalling activity and therefore on many cell functions, including migration and proliferation. Like other tyrosine kinase receptors (TKR), the insulin receptor (INSR) has been shown to be endocytosed by clathrin-dependent and -independent mechanisms. Once at the early endosome (EE), the sorting of the receptor, either to the late endosome (LE) for degradation or back to the PM through slow or fast recycling pathways, will determine the intensity and duration of insulin effects. Both the endocytic and the endosomic pathways are regulated by many proteins, the Arf and Rab families of small GTPases being some of the most relevant. Here, we argue for a specific role for the slow recycling route, whilst we review the main molecular mechanisms involved in INSR endocytosis, sorting and recycling, as well as their possible role in cell functions.

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