A Myosin IK-Abp1-PakB Circuit Acts as a Switch to Regulate Phagocytosis Efficiency

Dieckmann, Régis; Heyden, Yosuke von; Kistler, Claudia; Gopaldass, Navin Andréw; Hausherr, Stéphanie; Crawley, Scott W.; Schwarz, Eva C.; Diensthuber, Ralph P.; Côté, Graham P.; Tsiavaliaris, Georgios; Soldati, Thierry

doi:10.1091/mbc.e09-06-0485

Cited by 37 publications

(56 citation statements)

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“…Here, we characterized D. discoideum myosin-1C, in addition to its endocytotic roles Dieckmann et al, 2010), as a high-affinity MT-binding myosin that associates with the spindle throughout mitosis. We show that the myosin-1C tail domain affects the dynamic instability of MTs by protecting them from depolymerization.…”

Section: Introductionmentioning

confidence: 99%

Myosin-1C associates with microtubules and stabilizes the mitotic spindle during cell division

Rump

Scholz

Thiel

et al. 2011

Journal of Cell Science

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SummaryThe mitotic spindle in eukaryotic cells is composed of a bipolar array of microtubules (MTs) and associated proteins that are required during mitosis for the correct partitioning of the two sets of chromosomes to the daughter cells. In addition to the well-established functions of MT-associated proteins (MAPs) and MT-based motors in cell division, there is increasing evidence that the F-actin-based myosin motors are important mediators of F-actin-MT interactions during mitosis. Here, we report the functional characterization of the long-tailed class-1 myosin myosin-1C from Dictyostelium discoideum during mitosis. Our data reveal that myosin-1C binds to MTs and has a role in maintenance of spindle stability for accurate chromosome separation. Both myosin-1C motor function and taildomain-mediated MT-F-actin interactions are required for the cell-cycle-dependent relocalization of the protein from the cell periphery to the spindle. We show that the association of myosin-1C with MTs is mediated through the tail domain. The myosin-1C tail can inhibit kinesin motor activity, increase the stability of MTs, and form crosslinks between MTs and F-actin. These data illustrate that myosin-1C is involved in the regulation of MT function during mitosis in D. discoideum.

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Section: Introductionmentioning

confidence: 99%

Myosin-1C associates with microtubules and stabilizes the mitotic spindle during cell division

Rump

Scholz

Thiel

et al. 2011

Journal of Cell Science

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“…Together with the kinase PakB, MyoK and Abp1 build a regulatory switch that regulates the efficiency of uptake of large particles. These two proteins interact and couple actin dynamics to membrane deformation but exert opposite regulatory roles on phagocytic uptake (12,13). Compared with wild type cells, myoK-null mutants display 20% decrease whereas abp1-null display 35% increase in the rate and extent of uptake of large particles.…”

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confidence: 99%

“…Compared with wild type cells, myoK-null mutants display 20% decrease whereas abp1-null display 35% increase in the rate and extent of uptake of large particles. Despite their direct interaction, MyoK and Abp1 localize independently at the phagocytic cup and on early phagosomes (12). Like other class I myosins, MyoK is essential for the maintenance of resting cortical tension and provides a force to push on negatively curved membranes (12,13).…”

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confidence: 99%

“…Despite their direct interaction, MyoK and Abp1 localize independently at the phagocytic cup and on early phagosomes (12). Like other class I myosins, MyoK is essential for the maintenance of resting cortical tension and provides a force to push on negatively curved membranes (12,13). Although there is no evidence yet that MyoK might share these functions with other class I myosins, MyoB in Dictyostelium (14), and Myosin IB in human (15), for example, are involved in membrane trafficking in the pinocytic pathway, potentially contributing to membrane deformation both at the endosomal level and at the plasma membrane (16).…”

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The Balance in the Delivery of ER Components and the Vacuolar Proton Pump to the Phagosome Depends on Myosin IK in Dictyostelium

Dieckmann

Gueho

Monroy

et al. 2012

Molecular & Cellular Proteomics

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In Dictyostelium, the cytoskeletal proteins Actin binding protein 1 (Abp1) and the class I myosin MyoK directly interact and couple actin dynamics to membrane deformation during phagocytosis. Together with the kinase PakB, they build a regulatory switch that controls the efficiency of uptake of large particles. As a basis for further functional dissection, exhaustive phagosome proteomics was performed and established that about 1300 proteins participate in phagosome biogenesis. Then, quantitative and comparative proteomic analysis of phagosome maturation was performed to investigate the impact of the absence of MyoK or Abp1. Immunoblots and two-dimensional differential gel electrophoresis of phagosomes isolated from myoK-null and abp1-null cells were used to determine the relative abundance of proteins during the course of maturation. Immunoblot profiling showed that absence of Abp1 alters the maturation profile of its direct binding partners such as actin and the Arp2/3 complex, suggesting that Abp1 directly regulates actin dynamics at the phagosome. Comparative twodimensional differential gel electrophoresis analysis resulted in the quantification of mutant-to-wild type abundance ratios at all stages of maturation for over one hundred identified proteins. Coordinated temporal changes in these ratio profiles determined the classification of identified proteins into functional groups. Ratio profiling revealed that the early delivery of ER proteins to the phagosome was affected by the absence of MyoK and was coupled to a reciprocal imbalance in the delivery of the vacuolar proton pump and Rab11 GTPases. As direct functional consequences, a delayed acidification and a reduced intraphagosomal proteolysis were demonstrated in vivo in myoK-null cells. In conclusion, the absence of MyoK alters the balance of the contributions of the ER and an endo-lysosomal compartment, and slows down phagosome acidification as well as the speed and efficiency of particle degradation inside the phagosome. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.017608, 886 -900, 2012.Professional phagocytes, ranging from phagotrophic protozoa to specialized cells of the innate immune system such as macrophages, neutrophils, or dendritic cells, ingest and digest large particles (Ͼ 250 nm). Indeed, the core machineries acting in phagocytosis have been conserved as its basic purpose evolved from predation and feeding to antigen presentation (1). Particle recognition by the phagocytes initiate the internalization process and triggers remodeling of the plasma membrane and its underlying cytoskeleton, to project a circular cup-shaped lamella around the particle. The phagocytic cup finally encloses the particle into a de novo membranebound vacuole, the phagosome. Endomembrane compartments, such as early and late endosomes (2-4) and the endoplasmic reticulum (5), are recruited to provide membrane to form the phagosome. Modifications of the environment within the closed phagosome generates a microbicidal milieu and leads to particle degradation. M...

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“…Furthermore, there is a peak in the generation of PI(3,4)P 2 , although the significance of this particular phosphoinositide species production in Dictyostelium has yet to be elucidated since no specific binding proteins have been identified (Dormann et al, 2004). Similarly to mammalian phagocytosis, Dictyostelium uptake of budding yeast is thought to involve several unconventional myosins with, specifically, class-I myosins MyoK, MyoC and MyoB all shown to localise at the constriction point of a phagocytic cup (Dieckmann et al, 2010). MyoB and the Arp2/3 complex are enriched close to the phagosome membrane and concentrated around the neck region of the budded yeast being engulfed (Clarke et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

The motor protein myosin 1G functions in FcγR-mediated phagocytosis

Dart

Tollis

Bright

et al. 2012

Journal of Cell Science

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SummaryPhagocytosis is the force-dependent complex cellular process by which immune cells engulf particles. Although there has been considerable progress in understanding ligand-receptor-induced actin polymerisation in pushing the membrane around the particle, significantly less is known about how localised contractile activities regulate cup closure in coordination with the actin cytoskeleton. Herein, we show that the unconventional class-I myosin, myosin 1G (Myo1G) is localised at phagocytic cups following Fcc-receptor (FccR) ligation in macrophages. This progressive recruitment is dependent on the activity of phosphoinositide 3-kinase and is particularly important for engulfment of large particles. Furthermore, point mutations in the conserved pleckstrin homology-like domain of Myo1G abolishes the localisation of the motor protein at phagocytic cups and inhibits engulfment downstream of FccR. Binding of Myo1G to both F-actin and phospholipids might enable cells to transport phospholipids towards the leading edge of cups and to facilitate localised contraction for cup closure.

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A Myosin IK-Abp1-PakB Circuit Acts as a Switch to Regulate Phagocytosis Efficiency

Cited by 37 publications

References 50 publications

Myosin-1C associates with microtubules and stabilizes the mitotic spindle during cell division

Myosin-1C associates with microtubules and stabilizes the mitotic spindle during cell division

The Balance in the Delivery of ER Components and the Vacuolar Proton Pump to the Phagosome Depends on Myosin IK in Dictyostelium

The motor protein myosin 1G functions in FcγR-mediated phagocytosis

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