Myosin X is a downstream effector of PI(3)K during phagocytosis

  title={Myosin X is a downstream effector of PI(3)K during phagocytosis},
  author={Dianne Cox and Jonathan S. Berg and Michael Cammer and John O. Chinegwundoh and Benjamin M. Dale and Richard E. Cheney and Steven M. Greenberg},
  journal={Nature Cell Biology},
Phagocytosis is a phosphatidylinositol-3-OH-kinase (PI(3)K)-dependent process in macrophages. We identified Myo10 (Myosin-X), an unconventional myosin with pleckstrin homology (PH) domains, as a potential downstream target of PI(3)K. Myo10 was recruited to phagocytic cups in a wortmannin-sensitive manner. Expression of a truncation construct of Myo10 (Myo10 tail) in a macrophage cell line or cytosolic loading of anti-Myo10 antibodies in bovine alveolar macrophages inhibited phagocytosis. In… 

The motor protein myosin 1G functions in Fc&ggr;R-mediated phagocytosis

It is shown that the unconventional class-I myosin, myos in 1G (Myo1G) is localised at phagocytic cups following Fc&ggr;-receptor ligation in macrophages, and point mutations in the conserved pleckstrin homology-like domain of Myo 1G abolishes the localisation of the motor protein atPhagocytosis.

PtdIns (3,4,5) P3 Recruitment of Myo10 Is Essential for Axon Development

Mechanism studies demonstrated that the recruitment of Myo10 through its PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns) P3 was essential for axon formation and in vivo studies confirmed that Myo 10 was required for neuronal morphological transition during radial neuronal migration in the developmental neocortex.

Myosin-X: a MyTH-FERM myosin at the tips of filopodia

Exciting new studies have begun to reveal the structure and single-molecule properties of this intriguing myosin, as well as its mechanisms of regulation and induction of filopodia.

Myosin X.

  • H. Tokuo
  • Biology
    Advances in experimental medicine and biology
  • 2020
This chapter addresses the structure of the Myo10 gene; the molecular structure of Myosin X protein with its multiple domains; the regulation of actin structures induced in cells by Myo 10; the expression and function of Myo12 in vitro and in vivo; and the role of MyO10 in cancer.

Differential regulation of myosin X movements by its cargos, DCC and neogenin

Different regulatory roles on Myo X activity by its cargo proteins, DCC and neogenin are demonstrated, revealing different cellular functions of D CC and neogensin.

Phosphoinositide-3-kinase-independent contractile activities associated with Fcγ-receptor-mediated phagocytosis and macropinocytosis in macrophages

These PI3K-independent myosin-II-based contractile activities that squeeze phagocytic cups and curve ruffles therefore represent a third component activity of the actin cytoskeleton during phagcytosis and macropinocytosis.

Creatine Kinase–Mediated ATP Supply Fuels Actin-Based Events in Phagocytosis

It is proposed that CK-B activity in macrophages contributes to complement-induced F-actin assembly events in early phagocytosis by providing local ATP supply, most likely via effects on actin polymerization behavior.

Phosphoinositide3‐kinase regulates actin polymerization during delayed phagocytosis of Helicobacter pylori

It is concluded that Hp and IgG beads are ingested by distinct mechanisms and that PI3Ks regulate the actin cytoskeleton during slow phagocytosis of ulcerogenic Hp.

PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages.

Findings imply that a pathway involving PtdIns(3,4)P2, Lpd, and VASP mediates phagocytosis at the stage of particle engulfment, and vasodilator-stimulated phosphoprotein was identified as a key actin-regulatory protein mediating phagosome formation downstream of Lpd.

Expression of the unconventional myosin Myo1c alters sodium transport in M1 collecting duct cells.

Evaluation of enhanced green fluorescent protein-Myo1c constructs supports the importance of the IQ region in targeting the Myo1C to its respective cellular domain, consistent with Myo 1c participating in the regulation of the Na+ channel after ADH stimulation.



A Requirement for Phosphatidylinositol 3-Kinase in Pseudopod Extension*

Results indicate that one or more isoforms of PI 3 kinase are required for maximal pseudopod extension but not phagocytosis per se, and suggest that PI 3-kinase is required for coordinating exocytic membrane insertion and pseudobod extension.

Restricted Accumulation of Phosphatidylinositol 3-Kinase Products in a Plasmalemmal Subdomain during Fcγ Receptor-Mediated Phagocytosis

3′PI accumulation during phagocytosis was transient, terminating shortly after sealing of the phagosomal vacuole, and two factors contribute to the rapid disappearance of 3′PI: the dissociation of the type I PI3K from thephagosomal membrane and the persistent accumulation of phosphoinositide phosphatases.

Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes

Specific pathways linking heterotrimeric G proteins and Fcγ receptors to the actin-based cytoskeleton are poorly understood. To test a requirement for Rho family members in cytoskeletal events

A role for MARCKS, the alpha isozyme of protein kinase C and myosin I in zymosan phagocytosis by macrophages

It is proposed that PKC- dependent phosphorylation is an early signal required for zymosan phagocytosis and that MARCKS and PKC alpha have a role in phagosome maturation.

Dictyostelium myosin IK is involved in the maintenance of cortical tension and affects motility and phagocytosis.

The data indicate a distinctive role for MyoK in the maintenance and dynamics of the cell cortex and suggest a new form of actin crosslinker, as both binding sites reside within its motor domain and carry potential sites of regulation.

A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages

It is shown that PI 3-kinase is not necessary for receptor-mediated stimulation of pseudopod extension, but rather functions in the closure of macropinosomes and phagosomes into intracellular organelles.

A class VII unconventional myosin is required for phagocytosis

Modular components of phagocytosis

This review presents evidence that phagocytosis proceeds in discrete but coordinated stages and emphasizes that the signaling requirements for each of these is distinct.

A role for myosin VII in dynamic cell adhesion

Regulation of polymorphonuclear leukocyte phagocytosis by myosin light chain kinase after activation of mitogen-activated protein kinase.

Evaluated the effect of directly inhibiting myosin adenosine triphosphatase using 2,3-butanedione monoxime (BDM) and found that phagocytosis was inhibited by more than 90% but MLCK activity remained unaffected, consistent with the interpretation that MEK activates ERK, ERK2 then activates MLCk, and M LCK activates myOSin.