Rho GTPases and the Downstream Effectors Actin-related Protein 2/3 (Arp2/3) Complex and Myosin II Induce Membrane Fusion at Self-contacts

Sumida, Grant M.; Yamada, Sōichiro

doi:10.1074/jbc.m114.612168

Cited by 23 publications

(18 citation statements)

References 40 publications

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“…1C) [ 5 , 6]. Similar auto-fusion events recently were detected in vertebrate cells [ 50 , 51 ]. These known examples of auto-fusion are described below.…”

Section: Types Of Fission Fusion and Fusogenssupporting

confidence: 61%

Auto-fusion and the shaping of neurons and tubes

Soulavie

Sundaram

2016

Seminars in Cell & Developmental Biology

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Cells adopt specific shapes that are necessary for specific functions. For example, some neurons extend elaborate arborized dendrites that can contact multiple targets. Epithelial and endothelial cells can form tiny seamless unicellular tubes with an intracellular lumen. Recent advances showed that cells can auto-fuse to acquire those specific shapes. During auto-fusion, a cell merges two parts of its own plasma membrane. In contrast to cell-cell fusion or macropinocytic fission, which result in the merging or formation of two separate membrane bound compartments, auto-fusion preserves one compartment, but changes its shape. The discovery of auto-fusion in C. elegans was enabled by identification of specific protein fusogens, EFF-1 and AFF-1, that mediate cell-cell fusion. Phenotypic characterization of eff-1 and aff-1 mutants revealed that fusogen-mediated fusion of two parts of the same cell can be used to sculpt dendritic arbors, reconnect two parts of an axon after injury, or form a hollow unicellular tube. Similar auto-fusion events recently were detected in vertebrate cells, suggesting that auto-fusion could be a widely used mechanism for shaping neurons and tubes.

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“…1C) [ 5 , 6]. Similar auto-fusion events recently were detected in vertebrate cells [ 50 , 51 ]. These known examples of auto-fusion are described below.…”

Section: Types Of Fission Fusion and Fusogenssupporting

confidence: 61%

Auto-fusion and the shaping of neurons and tubes

Soulavie

Sundaram

2016

Seminars in Cell & Developmental Biology

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“…Addition of 20 μM ML141, a small molecule inhibitor of Cdc42 activity (51,52), resulted in a 65% decrease in Cdc42 activity (Fig. S5C) and a significant decrease in cell protrusive area and spreading on a 30-kPa Ecad-Fc PA gel; washout of ML141 resulted in the reestablishment of an elongated cell shape and the reappearance of large, flat lamellipodia with filopodia-like protrusions at both ends of the cell (Fig.…”

Section: Resultsmentioning

confidence: 99%

Changes in E-cadherin rigidity sensing regulate cell adhesion

Collins

Denisin

Pruitt

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Mechanical cues are sensed and transduced by cell adhesion complexes to regulate diverse cell behaviors. Extracellular matrix (ECM) rigidity sensing by integrin adhesions has been well studied, but rigidity sensing by cadherins during cell adhesion is largely unexplored. Using mechanically tunable polyacrylamide (PA) gels functionalized with the extracellular domain of E-cadherin (Ecad-Fc), we showed that E-cadherin-dependent epithelial cell adhesion was sensitive to changes in PA gel elastic modulus that produced striking differences in cell morphology, actin organization, and membrane dynamics. Traction force microscopy (TFM) revealed that cells produced the greatest tractions at the cell periphery, where distinct types of actin-based membrane protrusions formed. Cells responded to substrate rigidity by reorganizing the distribution and size of hightraction-stress regions at the cell periphery. Differences in adhesion and protrusion dynamics were mediated by balancing the activities of specific signaling molecules. Cell adhesion to a 30-kPa Ecad-Fc PA gel required Cdc42-and formin-dependent filopodia formation, whereas adhesion to a 60-kPa Ecad-Fc PA gel induced Arp2/3-dependent lamellipodial protrusions. A quantitative 3D cell-cell adhesion assay and live cell imaging of cell-cell contact formation revealed that inhibition of Cdc42, formin, and Arp2/3 activities blocked the initiation, but not the maintenance of established cell-cell adhesions. These results indicate that the same signaling molecules activated by E-cadherin rigidity sensing on PA gels contribute to actin organization and membrane dynamics during cell-cell adhesion. We hypothesize that a transition in the stiffness of E-cadherin homotypic interactions regulates actin and membrane dynamics during initial stages of cellcell adhesion.C ell adhesion is essential for tissue structure and function. Cells use specialized types of adhesions to interact with the surrounding environment, including integrin-based focal adhesions at cell-extracellular matrix (cell-ECM) contacts and cadherin-based adhesions at cell-cell contacts (1). Integrins bind to the ECM and intracellular proteins that link to the actin cytoskeleton and important signaling pathways (2). Similarly, cadherins regulate cellcell recognition and adhesion (3) and, through cytoplasmic adaptor proteins (catenins, vinculin) (4, 5), also link to the actin cytoskeleton and other proteins with signaling and scaffolding functions (6).Initiation of cell-cell adhesion requires significant reorganization of the actin cytoskeleton and is tightly controlled by the activities of actin nucleating proteins and Rho GTPases. Adhesion is initiated when filopodia from opposing cells come into contact with one another (7,8), and this process is regulated by Cdc42 activity (9, 10) and formin-dependent actin polymerization (11)(12)(13)(14). Intermediate stages of cell-cell contact formation involve lateral expansion of the contact by Rac1-induced and Arp2/3-dependent lamellipodial activity (15, 16). Finally, com...

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“…As functional actin filaments may play a role in NET formation (41), it is possible that cytochalasin B interfered with NET and antimicrobial protein release in our study and thus prevented bacterial killing. However, other known inhibitors of phagocytosis and endocytosis, such as latrunculin A or CK666, also exert their effects by disturbing actin polymerization (42,43). Future experiments may be directed at investigating differences among such inhibitors regarding their interference with NET release.…”

Section: Figmentioning

confidence: 99%

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

et al. 2017

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Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii, stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated.KEYWORDS neutrophils, NETs, reactive oxygen species, periodontitis, oral bacteria P eriodontitis is initiated by the accumulation of microbial biofilms at and below the gingival margin. Indeed, it has been estimated that ϳ700 oral bacterial species and ϳ1,200 predominant phylotypes exist (1-3). Of these bacterial species, 5 major bacterial complexes (red, orange, yellow, green, and purple) have been identified by Socransky et al. using DNA probes (4) and are referred to here as Socransky complexes. The clustering and ordination analysis allowed them to assign microbial species to a color complex on the basis of the strength of the association with each other and the clinical staging of periodontitis. The biofilms which develop during disease are orchestrated to maximize their adherence, communication, and survival. The accumulation of bacterial species within the biofilm enables its development and perseverance, and certain bacteria, such as Fusobacterium nucleatum, are key orchestrators of biofilm formation and maturation (5).In susceptible individuals, dysbiosis and an aberrant host-microbe equilibrium can result in the onset of disease (6), where the microbial biofilm thrives by exploiting the

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Rho GTPases and the Downstream Effectors Actin-related Protein 2/3 (Arp2/3) Complex and Myosin II Induce Membrane Fusion at Self-contacts

Cited by 23 publications

References 40 publications

Auto-fusion and the shaping of neurons and tubes

Auto-fusion and the shaping of neurons and tubes

Changes in E-cadherin rigidity sensing regulate cell adhesion

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

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