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A myosin IK-Abp1-PakB circuit acts as a switch to regulate phagocytosis efficiency

von Heyden, Yosuke
Kistler, Claudia
Crawley, Scott William
Schwarz, Eva C
Diensthuber, Ralph P
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Published in Molecular biology of the cell. 2010, vol. 21, no. 9, p. 1505-18
Abstract Actin dynamics and myosin (Myo) contractile forces are necessary for formation and closure of the phagocytic cup. In Dictyostelium, the actin-binding protein Abp1 and myosin IK are enriched in the closing cup and especially at an actin-dense constriction furrow formed around the neck of engulfed budded yeasts. This phagocytic furrow consists of concentric overlapping rings of MyoK, Abp1, Arp3, coronin, and myosin II, following an order strikingly reminiscent of the overall organization of the lamellipodium of migrating cells. Mutation analyses of MyoK revealed that both a C-terminal farnesylation membrane anchor and a Gly-Pro-Arg domain that interacts with profilin and Abp1 were necessary for proper localization in the furrow and efficient phagocytosis. Consequently, we measured the binding affinities of these interactions and unraveled further interactions with profilins, dynamin A, and PakB. Due to the redundancy of the interaction network, we hypothesize that MyoK and Abp1 are restricted to regulatory roles and might affect the dynamic of cup progression. Indeed, phagocytic uptake was regulated antagonistically by MyoK and Abp1. MyoK is phosphorylated by PakB and positively regulates phagocytosis, whereas binding of Abp1 negatively regulates PakB and MyoK. We conclude that a MyoK-Abp1-PakB circuit acts as a switch regulating phagocytosis efficiency of large particles.
Keywords AnimalsDictyostelium/genetics/metabolism/ultrastructureGreen Fluorescent Proteins/genetics/metabolismImmunoblottingMicrofilament Proteins/genetics/metabolismMicroscopy, ElectronMicroscopy, FluorescenceMutationMyosin Type I/genetics/metabolismPhagocytosis/physiologyPhosphorylationProtein BindingProtein Kinases/genetics/metabolismProtein PrenylationProtozoan Proteins/genetics/metabolismRecombinant Fusion Proteins/genetics/metabolismSurface Plasmon ResonanceYeasts/physiology/ultrastructure
PMID: 20200225
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DIECKMANN, Régis et al. A myosin IK-Abp1-PakB circuit acts as a switch to regulate phagocytosis efficiency. In: Molecular biology of the cell, 2010, vol. 21, n° 9, p. 1505-18. https://archive-ouverte.unige.ch/unige:18877

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Deposited on : 2012-03-19

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