title: A myosin IK-Abp1-PakB circuit acts as a switch to regulate phagocytosis efficiency.
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.
authors.affiliation: Départment de Biochimie, Faculté des Sciences, Université de Genève, Sciences II, CH-1211-Genève-4, Switzerland.
authors.forename: Régis
authors.initials: R
authors.lastname: Dieckmann
authors.forename: Yosuke
authors.initials: Y
authors.lastname: von Heyden
authors.forename: Claudia
authors.initials: C
authors.lastname: Kistler
authors.forename: Navin
authors.initials: N
authors.lastname: Gopaldass
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hausherr
authors.forename: Scott William
authors.initials: SW
authors.lastname: Crawley
authors.forename: Eva C
authors.initials: EC
authors.lastname: Schwarz
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Diensthuber
authors.forename: Graham P
authors.initials: GP
authors.lastname: Côté
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsiavaliaris
authors.forename: Thierry
authors.initials: T
authors.lastname: Soldati
mesh_terms: D000818:Animals; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009154:Mutation; D024461:Myosin Type I / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017368:Protein Prenylation; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance; D015003:Yeasts / Q000502:physiology / Q000648:ultrastructure
chemical_list: D008840:Microfilament Proteins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; C093485:110 kDa protein kinase, Dictyostelium; D024461:Myosin Type I