Motorized RhoGAP myosin IXb (Myo9b) controls cell shape and motility

Hanley, Peter J.; Xu, Yan; Kronlage, Moritz; Grobe, Kay; Schön, Peter; Song, Jian; Sorokin, Lydia; Schwab, Albrecht; Bähler, Martin

doi:10.1073/pnas.0911986107

Cited by 107 publications

(149 citation statements)

References 44 publications

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“…The two class IX myosins in mammals, Myo9a 2 and Myo9b, exist in multiple splice variants (2). Myo9a has been shown to play a role in epithelial differentiation and morphology whereas Myo9b regulates the migration of macrophages and possibly other immune cells (3,4). Class IX myosins share a similar structure with the myosins of the other classes, containing a head region, a calmodulin/light chain-binding domain, and a tail region.…”

mentioning

confidence: 95%

Head of Myosin IX Binds Calmodulin and Moves Processively toward the Plus-end of Actin Filaments

Liao¹,

Elfrink²,

Bähler³

2010

Journal of Biological Chemistry

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Mammalian myosin IXb (Myo9b) has been shown to exhibit unique motor properties in that it is a single-headed processive motor and the rate-limiting step in its chemical cycle is ATP hydrolysis. Furthermore, it has been reported to move toward the minus-and the plus-end of actin filaments. To analyze the contribution of the light chain-binding domain to the movement, processivity, and directionality of a single-headed processive myosin, we expressed constructs of Caenorhabditis elegans myosin IX (Myo9) containing either the head (Myo9-head) or the head and the light chain-binding domain (Myo9-head-4IQ). Both constructs supported actin filament gliding and moved toward the plus-end of actin filaments. We identified in the head of class IX myosins a calmodulin-binding site at the N terminus of loop 2 that is unique among the myosin superfamily members. Ca 2؉ /calmodulin negatively regulated ATPase and motility of the Myo9-head. The Myo9-head demonstrated characteristics of a processive motor in that it supported actin filament gliding and pivoting at low motor densities. Quantum dot-labeled Myo9-head moved along actin filaments with a considerable run length and frequently paused without dissociating even in the presence of obstacles. We conclude that class IX myosins are plus-end-directed motors and that even a single head exhibits characteristics of a processive motor.Myosins form a large superfamily of actin-based molecular motors that is composed of at least 35 classes (1). Class IX myosins arose in metazoa after the separation of the fungi (1). Invertebrates contain a single myosin class IX gene with the exception of the Drosophila species that have lost their class IX myosin. Bony fishes contain four myosin IX genes and other vertebrates, including mammalia two genes. The two class IX myosins in mammals, Myo9a 2 and Myo9b, exist in multiple splice variants (2). Myo9a has been shown to play a role in epithelial differentiation and morphology whereas Myo9b regulates the migration of macrophages and possibly other immune cells (3, 4). Class IX myosins share a similar structure with the myosins of the other classes, containing a head region, a calmodulin/light chain-binding domain, and a tail region.Additionally, class IX myosins carry some unique features, including a large N-terminal extension preceding the head domain and a long insertion within the head domain in loop 2. The tail region comprises a C1 zinc-binding domain and a RhoGAP domain. Because of this RhoGAP domain, class IX myosins are involved in signal transduction regulating the dynamics of the actin cytoskeleton (2, 5).Mammalian Myo9b, the only class IX myosin studied so far in vitro, exhibits unique mechano-chemical properties. It has been reported to take multiple successive steps along actin filaments without dissociating, indicating that it is a processive motor (6 -8). This is remarkable because Myo9b is a singleheaded myosin. Other myosins that move processively on actin filaments, such as myosin V, dimeric myosin VI, and myosin VII, are two-...

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confidence: 95%

Head of Myosin IX Binds Calmodulin and Moves Processively toward the Plus-end of Actin Filaments

Liao¹,

Elfrink²,

Bähler³

2010

Journal of Biological Chemistry

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“…S100A4 deficiency leads to a defective CSF-1 chemotactic response, owing to reduced persistence and size of membrane protrusions associated with persistent and enhanced actomyosin-IIA assembly and hyperphosphorylation and mislocalization of paxillin (Li et al 2010). The small GTPase Rho is required for CSF-1-mediated macrophage chemotaxis ) and promotes tail retraction by controlling myosin activity (Hanley et al 2010). In macrophages stimulated with CSF-1, Rho undergoes cycles of activation and deactivation.…”

Section: Csf-1 Receptor Signaling In Myeloid Cellsmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

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485

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The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.

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“…Ϫ/Ϫ Macrophages-The motorized RhoGAP Myo9b is a key negative regulator of Rho in leukocytes (1,38). We next tested whether genetic deletion of RhoB rescued the motility defect of macrophages lacking Myo9b (1).…”

Section: Deletion Of Rhob Partially Rescues the Motility Defect Of Myo9bmentioning

confidence: 99%

“…Like most cells, neutrophils and macrophages move on a two-dimensional surface by generating thin membrane protrusions at the front, followed by pulling forward of the cell body and retraction of the back end (1,2), along the lines of the motility model first delineated by Abercrombie et al (3) in the early 1970s (reviewed in Ref. 4).…”

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Mouse Macrophages Completely Lacking Rho Subfamily GTPases (RhoA, RhoB, and RhoC) Have Severe Lamellipodial Retraction Defects, but Robust Chemotactic Navigation and Altered Motility

Königs

Jennings

Vogl

et al. 2014

Journal of Biological Chemistry

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Background:RhoA is strongly implicated in cell motility. Results: Macrophages lacking RhoA or RhoB have mild phenotypes, whereas double mutants, which also lack RhoC, exhibit severe cytoskeletal defects, but robust chemotaxis. Conclusion: RhoA and RhoB have overlapping functions in tail and lamellipodial membrane retraction, but are not critical for motility. Significance: The Rho subfamily is largely redundant for "front end" functions of motility and chemotaxis.

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Motorized RhoGAP myosin IXb (Myo9b) controls cell shape and motility

Cited by 107 publications

References 44 publications

Head of Myosin IX Binds Calmodulin and Moves Processively toward the Plus-end of Actin Filaments

Head of Myosin IX Binds Calmodulin and Moves Processively toward the Plus-end of Actin Filaments

CSF-1 Receptor Signaling in Myeloid Cells

Mouse Macrophages Completely Lacking Rho Subfamily GTPases (RhoA, RhoB, and RhoC) Have Severe Lamellipodial Retraction Defects, but Robust Chemotactic Navigation and Altered Motility

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