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Mark S. Mooseker - One of the best experts on this subject based on the ideXlab platform.
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membrane cytoskeletal crosstalk mediated by myosin i regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.
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Membrane-cytoskeletal crosstalk mediated by myosin-I regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Qingsen Li, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.Phagocytosis of pathogens is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface. Here authors show that myosin 1e and myosin 1f link the actin cytoskeleton to the membrane and are required for efficient phagocytosis of antibody-opsonized targets.
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membrane cytoskeleton mechanical feedback mediated by myosin i controls phagocytic efficiency
bioRxiv, 2018Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W Oakes, Mira KrendelAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We have found that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we found that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a novel role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a model for a membrane-tension based feedback mechanism for phagocytic cup closure.
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Class V Myosins.
Biochimica et biophysica acta, 2000Co-Authors: Samara L. Reck-peterson, Mark S. Mooseker, D. William Provance, John A. MercerAbstract:1. IntroductionThe myosin family of actin-based molecular mo-tors consists of 15 known classes that are structurallydistinct based on comparisons of the primary struc-ture of the motor domains of the known myosinheavy chain genes [1^3]. Information regarding thefunction and/or biochemical properties of most ofthese myosin classes is sparse relative to the well-characterized class II and class I Myosins; neverthe-less, the range of proposed functions for these myo-sins is already remarkably broad [1]. There are anumber of recent reviews that provide an overviewof the rapidly growing myosin gene family [1,4^8].Among the best characterized and functionally di-verse of the recently discovered myosin classes arethe class V Myosins, the focus of this review (forother reviews see [9^11]).Myosin-V was initially characterized as an unusualcalmodulin binding protein from brain with a num-ber of myosin-like biochemical properties [12^14].Subsequently, myosin-V heavy chain genes werecloned from mouse, yeast and chicken, thus de¢ningthe ¢fth class of actin-based motors [15^19]. Studiesof the mouse and yeast class V Myosins provided the¢rst insights regarding the cellular function of myo-sin-V. Phenotypes of the mutant dilute mouse andthe temperature-sensitive yeast mutant, myo2-66 ledto the hypothesis that class V Myosins may functionin cell polarity and membrane tra⁄cking [15,16].Moreover, mutations in the human ortholog of thedilute heavy chain gene cause Griscelli syndrome, arare recessive disease characterized by pigmentarydilution and in most, but not all cases immunode¢-ciency [20^22]. Neurological disorders have also beenreported in Griscelli syndrome patients [22,23]. Sincethese ¢rst studies, a great deal has been learnedabout the biochemistry, biophysics and cellular func-tion of the class V Myosins. This review will discussthe emerging evidence that myosin-V is a processiveactin-based motor that has multiple functions in thecell ranging from mRNA transport, cell polarity andmembrane tra⁄cking.There are currently nine complete myosin-V heavychain sequences known (Fig. 1). Analysis of the twocompleted eukaryotic genomes of Saccharomyces ce-revisiae and Caenorhabditis elegans reveals that yeasthave two class V Myosins, while C. elegans has asingle class V myosin heavy chain gene. In verte-brates, there are at least three distinct subclasses ofmyosin-V. The three most closely related heavy chainsequences, that of chicken brain myosin-V, the
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Localization of unconventional Myosins V and VI in neuronal growth cones
Journal of Neurobiology, 2000Co-Authors: Daniel M. Suter, Paul Forscher, Foued Salmen Espindola, Mark S. MoosekerAbstract:Class V and VI Myosins, two of the six known classes of actin-based motor genes expressed in vertebrate brain (Class I, II, V, VI, IX, and XV), have been suggested to be organelle motors. In this report, the neuronal expression and subcellular localization of chicken brain myosin V and myosin VI is examined. Both Myosins are expressed in brain during embryogenesis. In cultured dorsal root ganglion (DRG) neurons, immunolocalization of myosin V and myosin VI revealed a similar distribution for these two Myosins. Both are present within cell bodies, neurites and growth cones. Both of these Myosins exhibit punctate labeling patterns that are found in the same subcellular region as microtubules in growth cone central domains. In peripheral growth cone domains, where individual puncta are more readily resolved, we observe a similar number of myosin V and myosin VI puncta. However, less than 20% of myosin V and myosin VI puncta colocalize with each other in the peripheral domains. After live cell extraction, punctate staining of myosin V and myosin VI is reduced in peripheral domains. However, we do not detect such changes in the central domains, suggesting that these Myosins are associated with cytoskeletal/organelle structures. In peripheral growth cone domains myosin VI exhibits a higher extractability than myosin V. This difference between myosin V and VI was also found in a biochemical growth cone particle preparation from brain, suggesting that a significant portion of these two motors has a distinct subcellular distribution. © 2000 John Wiley & Sons, Inc. J Neurobiol 42: 370–382, 2000
Patrick W Oakes - One of the best experts on this subject based on the ideXlab platform.
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Membrane-cytoskeletal crosstalk mediated by myosin-I regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Qingsen Li, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.Phagocytosis of pathogens is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface. Here authors show that myosin 1e and myosin 1f link the actin cytoskeleton to the membrane and are required for efficient phagocytosis of antibody-opsonized targets.
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membrane cytoskeletal crosstalk mediated by myosin i regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.
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membrane cytoskeleton mechanical feedback mediated by myosin i controls phagocytic efficiency
bioRxiv, 2018Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W Oakes, Mira KrendelAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We have found that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we found that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a novel role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a model for a membrane-tension based feedback mechanism for phagocytic cup closure.
Valerian V Dolja - One of the best experts on this subject based on the ideXlab platform.
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Myosins viii and xi play distinct roles in reproduction and transport of tobacco mosaic virus
PLOS Pathogens, 2014Co-Authors: Khalid Amari, Valerian V Dolja, Martin Di Donato, Manfred HeinleinAbstract:Viruses are obligatory parasites that depend on host cellular factors for their replication as well as for their local and systemic movement to establish infection. Although myosin motors are thought to contribute to plant virus infection, their exact roles in the specific infection steps have not been addressed. Here we investigated the replication, cell-to-cell and systemic spread of Tobacco mosaic virus (TMV) using dominant negative inhibition of myosin activity. We found that interference with the functions of three class VIII Myosins and two class XI Myosins significantly reduced the local and long-distance transport of the virus. We further determined that the inactivation of Myosins XI-2 and XI-K affected the structure and dynamic behavior of the ER leading to aggregation of the viral movement protein (MP) and to a delay in the MP accumulation in plasmodesmata (PD). The inactivation of myosin XI-2 but not of myosin XI-K affected the localization pattern of the 126k replicase subunit and the level of TMV accumulation. The inhibition of Myosins VIII-1, VIII-2 and VIII-B abolished MP localization to PD and caused its retention at the plasma membrane. These results suggest that class XI Myosins contribute to the viral propagation and intracellular trafficking, whereas Myosins VIII are specifically required for the MP targeting to and virus movement through the PD. Thus, TMV appears to recruit distinct Myosins for different steps in the cell-to-cell spread of the infection.
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class xi Myosins are required for development cell expansion and f actin organization in arabidopsis
The Plant Cell, 2010Co-Authors: Valera V Peremyslov, Alexey I Prokhnevsky, Valerian V DoljaAbstract:The actomyosin system is conserved throughout eukaryotes. Although F-actin is essential for cell growth and plant development, roles of the associated Myosins are poorly understood. Using multiple gene knockouts in Arabidopsis thaliana, we investigated functional profiles of five class XI Myosins, XI-K, XI-1, XI-2, XI-B, and XI-I. Plants lacking three Myosins XI showed stunted growth and delayed flowering, whereas elimination of four Myosins further exacerbated these defects. Loss of Myosins led to decreased leaf cell expansion, with the most severe defects observed in the larger leaf cells. Root hair length in myosin-deficient plants was reduced ∼10-fold, with quadruple knockouts showing morphological abnormalities. It was also found that trafficking of Golgi and peroxisomes was entirely myosin dependent. Surprisingly, Myosins were required for proper organization of F-actin and the associated endoplasmic reticulum networks, revealing a novel, architectural function of the class XI Myosins. These results establish critical roles of myosin-driven transport and F-actin organization during polarized and diffuse cell growth and indicate that Myosins are key factors in plant growth and development.
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overlapping functions of the four class xi Myosins in arabidopsis growth root hair elongation and organelle motility
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Alexey I Prokhnevsky, Valera V Peremyslov, Valerian V DoljaAbstract:Flowering plants have evolved multigene families of the class XI myosin motors, the functions of which remain poorly understood. Here, we investigated functional profiles of the Arabidopsis Myosins that belong to two paralogous pairs, XI-K/XI-1 and XI-2/XI-B, using single and double gene-knockout mutants. It was found that the Myosins XI-K, XI-2, and XI-B, but not XI-1 have overlapping and additive roles in the root hair elongation. A nonidentical set of the three Myosins, XI-K, XI-1, and XI-2, exhibited partially redundant and additive roles in the transport of Golgi stacks, peroxisomes, and mitochondria. Conspicuously, the double xi-k/1 knockout plants that showed the largest cumulative reduction of the organelle velocities also exhibited a stunted plant growth and reduced fecundity phenotype. Collectively, these results suggest that the rapid, myosin-powered organelle trafficking is required for the optimal plant growth, whereas a distinct myosin function, presumably the vesicular transport, is involved in elongation of the root hairs. In addition, our data imply that the myosin gene duplication in plants has been followed by a gradual functional specialization of the resulting pairs of myosin paralogs.
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two class xi Myosins function in organelle trafficking and root hair development in arabidopsis
Plant Physiology, 2008Co-Authors: Valera V Peremyslov, Alexey I Prokhnevsky, Dror Avisar, Valerian V DoljaAbstract:Multigene families encoding class XI Myosins are conserved in higher plants, however, little information is available on specific functions of these ubiquitous molecular motors. We isolated gene knockout mutants for all 13 class XI Myosins present in Arabidopsis (Arabidopsis thaliana) genome. Inactivation of 11 myosin genes resulted in no discernible phenotypes under the normal growth conditions. In contrast, the knockouts of the remaining two myosin genes, XI-2 (formerly MYA2) and XI-K, exhibited similar defects in root hair elongation suggesting that the myosin-driven motility plays a significant role in a polar tip growth. Strikingly, inactivation of each of these Myosins also reduced trafficking of Golgi stacks, peroxisomes, and mitochondria in root hairs and in leaf epidermal cells. These results indicate that Myosins XI-K and XI-2 play major and overlapping roles in the cell dynamics in Arabidopsis and highlight the redundant nature of myosin function in plants.
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myosin xi k is required for rapid trafficking of golgi stacks peroxisomes and mitochondria in leaf cells of nicotiana benthamiana
Plant Physiology, 2008Co-Authors: Dror Avisar, Alexey I Prokhnevsky, Kira S Makarova, Eugene V Koonin, Valerian V DoljaAbstract:A prominent feature of plant cells is the rapid, incessant movement of the organelles traditionally defined as cytoplasmic streaming and attributed to actomyosin motility. We sequenced six complete Nicotiana benthamiana cDNAs that encode class XI and class VIII Myosins. Phylogenetic analysis indicates that these two classes of Myosins diverged prior to the radiation of green algae and land plants from a common ancestor and that the common ancestor of land plants likely possessed at least seven Myosins. We further report here that movement of Golgi stacks, mitochondria, and peroxisomes in the leaf cells of N. benthamiana is mediated mainly by myosin XI-K. Suppression of myosin XI-K function using dominant negative inhibition or RNA interference dramatically reduced movement of each of these organelles. When similar approaches were used to inhibit functions of myosin XI-2 or XI-F, only moderate to marginal effects were observed. Organelle trafficking was virtually unaffected in response to inhibition of each of the three class VIII Myosins. Interestingly, none of the tested six Myosins appears to be involved in light-induced movements of chloroplasts. Taken together, these data strongly suggest that myosin XI-K has a major role in trafficking of Golgi stacks, mitochondria, and peroxisomes, whereas Myosins XI-2 and XI-F might perform accessory functions in this process. In addition, our analysis of thousands of individual organelles revealed independent movement patterns for Golgi stacks, mitochondria, and peroxisomes, indicating that the notion of coordinated cytoplasmic streaming is not generally applicable to higher plants.
Richard A Flavell - One of the best experts on this subject based on the ideXlab platform.
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Membrane-cytoskeletal crosstalk mediated by myosin-I regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Qingsen Li, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.Phagocytosis of pathogens is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface. Here authors show that myosin 1e and myosin 1f link the actin cytoskeleton to the membrane and are required for efficient phagocytosis of antibody-opsonized targets.
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membrane cytoskeletal crosstalk mediated by myosin i regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.
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membrane cytoskeleton mechanical feedback mediated by myosin i controls phagocytic efficiency
bioRxiv, 2018Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W Oakes, Mira KrendelAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We have found that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we found that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a novel role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a model for a membrane-tension based feedback mechanism for phagocytic cup closure.
Sarah R. Barger - One of the best experts on this subject based on the ideXlab platform.
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Membrane-cytoskeletal crosstalk mediated by myosin-I regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Qingsen Li, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.Phagocytosis of pathogens is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface. Here authors show that myosin 1e and myosin 1f link the actin cytoskeleton to the membrane and are required for efficient phagocytosis of antibody-opsonized targets.
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membrane cytoskeletal crosstalk mediated by myosin i regulates adhesion turnover during phagocytosis
Nature Communications, 2019Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, John M Heddleston, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W OakesAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.
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membrane cytoskeleton mechanical feedback mediated by myosin i controls phagocytic efficiency
bioRxiv, 2018Co-Authors: Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Paolo Maiuri, Tatyana Svitkina, Mark S. Mooseker, Richard A Flavell, Patrick W Oakes, Mira KrendelAbstract:Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We have found that two actin-dependent molecular motors, class 1 Myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we found that without the actin-membrane linkage mediated by these Myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a novel role for class 1 Myosins in coordinated adhesion turnover during phagocytosis and supports a model for a membrane-tension based feedback mechanism for phagocytic cup closure.
