Competition between Blown Fuse and WASP for WIP Binding Regulates the Dynamics of WASP-Dependent Actin Polymerization In Vivo

Jin, Peng; Duan, Rui; Luo, Fengbao; Zhang, Guofeng; Hong, Sabrina N.; Chen, Elizabeth H.

doi:10.1016/j.devcel.2011.04.007

Cited by 59 publications

(112 citation statements)

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“…N-WASp Is Required in both Fusing Partners. A recurrent issue in studies of both Drosophila and mammalian myoblast fusion, with broad mechanistic implications, is whether fusion-related elements function in one or both fusing myogenic cells (19)(20)(21)(22)(23). We therefore used the N-WASp fl/fl -derived satellite-cell cultures to assess the requirement for N-WASp in this context.…”

Section: Conditional Disruption Of Murine N-wasp Results In Abnormal mentioning

confidence: 99%

The actin regulator N-WASp is required for muscle-cell fusion in mice

Gruenbaum-Cohen

Harel²,

Umansky³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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A fundamental aspect of skeletal myogenesis involves extensive rounds of cell fusion, in which individual myoblasts are incorporated into growing muscle fibers. Here we demonstrate that N-WASp, a ubiquitous nucleation-promoting factor of branched microfilament arrays, is an essential contributor to skeletal muscle-cell fusion in developing mouse embryos. Analysis both in vivo and in primary satellite-cell cultures, shows that disruption of N-WASp function does not interfere with the program of skeletal myogenic differentiation, and does not affect myoblast motility, morphogenesis and attachment capacity. N-WASp-deficient myoblasts, however, fail to fuse. Furthermore, our analysis suggests that myoblast fusion requires N-WASp activity in both partners of a fusing myoblast pair. These findings reveal a specific role for N-WASp during mammalian myogenesis. WASp-family elements appear therefore to act as universal mediators of the myogenic cell-cell fusion mechanism underlying formation of functional muscle fibers, in both vertebrate and invertebrate species.actin nucleation | myotube formation

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Section: Conditional Disruption Of Murine N-wasp Results In Abnormal mentioning

confidence: 99%

The actin regulator N-WASp is required for muscle-cell fusion in mice

Gruenbaum-Cohen

Harel²,

Umansky³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…As in scar or kette mutants, embryos mutant for blow exhibit larger actin foci (Richardson et al, 2007;Jin et al, 2011). These large foci appear to reflect a slower exchange rate of G-actin, in addition to higher levels of Vrp1/WASp at points of cell-cell contact (Jin et al, 2011).…”

Section: F-actin Foci F-actin Nucleating Complexes and Fusion Poresmentioning

confidence: 99%

“…Crk also binds to the FCM-specific Blow protein, and can recruit it to points of fusion (Jin et al, 2011). Blow functions in this location to modulate the stability of the Vrp1/WASp complex, by competing with WASp for Vrp1 binding (Jin et al, 2011). As in scar or kette mutants, embryos mutant for blow exhibit larger actin foci (Richardson et al, 2007;Jin et al, 2011).…”

Section: F-actin Foci F-actin Nucleating Complexes and Fusion Poresmentioning

confidence: 99%

“…As evidenced by identification of the FCM-specific Vrp1/WASp complex (Kim et al, 2007;Massarwa et al, 2007) and by FCMexclusive expression of Blow (Jin et al, 2011), studies have established the molecular asymmetry between the founder cells and FCMs. Recent studies have also shown that, despite ubiquitous expression (Erickson et al, 1997), the Rac1 GEF Mbc and active Rac1 are asymmetrically distributed in the FCMs at points of cellcell contact (Haralalka et al, 2011).…”

Section: Reviewmentioning

confidence: 99%

“…5). Crk also binds to the FCM-specific Blow protein, and can recruit it to points of fusion (Jin et al, 2011). Blow functions in this location to modulate the stability of the Vrp1/WASp complex, by competing with WASp for Vrp1 binding (Jin et al, 2011).…”

Section: F-actin Foci F-actin Nucleating Complexes and Fusion Poresmentioning

confidence: 99%

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Myoblast fusion: lessons from flies and mice

2012

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The fusion of myoblasts into multinucleate syncytia plays a fundamental role in muscle function, as it supports the formation of extended sarcomeric arrays, or myofibrils, within a large volume of cytoplasm. Principles learned from the study of myoblast fusion not only enhance our understanding of myogenesis, but also contribute to our perspectives on membrane fusion and cell-cell fusion in a wide array of model organisms and experimental systems. Recent studies have advanced our views of the cell biological processes and crucial proteins that drive myoblast fusion. Here, we provide an overview of myoblast fusion in three model systems that have contributed much to our understanding of these events: the Drosophila embryo; developing and regenerating mouse muscle; and cultured rodent muscle cells. IntroductionThe process of fusing two adjacent membranes accomplishes many goals that are crucial to the development and maintenance of living organisms. Broadly, membrane fusion can occur intracellularly, as with synaptic vesicles, or between cells, as for sperm-egg fusion. Cell fusion occurs in a broad range of organisms, including Saccharomyces cerevisiae and Caenorhabditis elegans, and between several cell types, such as macrophages, placental trophoblasts and myoblasts. Experimental analysis of fusion in these systems has revealed the involvement of a diverse array of specialized molecules.Myoblast fusion, a fundamental step in the differentiation of muscle in most organisms, can involve tens of thousands of myoblasts, Given the complexity of the musculature, fusion must be a regulated process in which the appropriate number of cells fuse at the appropriate time and place. Often these cells migrate long distances prior to fusion, and fusion can involve multiple cell types, necessitating cell recognition and adhesion, which are crucial to accurate and efficient fusion. In addition to the early fusion events that occur during embryogenesis, vertebrate muscle tissue is able to regenerate in response to damage and disease. This regeneration involves proliferation of muscle satellite cells (see Glossary, Box 1) and their subsequent fusion to repair the damaged muscles. The focus of this review is the process of myoblast fusion, which involves cell migration, adhesion and signaling transduction pathways leading up to the actual fusion event. We review the crucial role of the actin cytoskeleton and actin polymerizing proteins, and recently revealed membrane protrusions that may drive fusion itself. We describe three powerful systems for this analysis: Drosophila embryogenesis; mouse embryogenesis and regeneration; and rodent tissue culture. We highlight the genes and morphological events involved in myoblast fusion, as revealed by each system. With the emergence of Danio rerio as another model for myoblast fusion, we also list relevant homologs in this system (Tables 1, 2). Experimental systems for the analysis of myoblast fusionThe ability to isolate and propagate mammalian myoblasts that could differentiate and fuse in...

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News in fusion

Lübke¹,

Löwer²,

Papendieken³

et al. 2019

Biologie in unserer Zeit

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Zusammenfassung Die Bildung eines synzytialen Muskels beruht auf der Fähigkeit von einkernigen Myoblasten zu fusionieren. Wesentliche Prozesse während der Myoblastenfusion von Drosophila und Säugetieren sind dabei die Zellerkennung und Zelladhäsion, die Bildung eines Zug‐ und Druckkräfte generierenden Zentrums durch Polymerisation von monomerem zu F‐Aktin, die Bildung einer Fusionspore sowie die Vermischung des Zytoplasmas und die Integration der Myoblasten in die wachsende Myotube. In den letzten 20 Jahren wurden viele Schlüsselgene der Myoblastenfusion am Modellorganismus Drosophila melanogaster identifiziert. Keines dieser Gene kodiert für ein Fusogen. Im Gegensatz dazu wurden in den letzten Jahren bei Mäusen zwei Proteine identifiziert, die direkt an der Umstrukturierung der Plasmamembran während der Bildung einer Fusionspore beteiligt sind und die fusogene Eigenschaften besitzen. Diese Proteine können uns zukünftig helfen zu verstehen, was während der Myoblastenfusion an der Zellmembran passiert.

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Competition between Blown Fuse and WASP for WIP Binding Regulates the Dynamics of WASP-Dependent Actin Polymerization In Vivo

Cited by 59 publications

References 50 publications

The actin regulator N-WASp is required for muscle-cell fusion in mice

The actin regulator N-WASp is required for muscle-cell fusion in mice

Myoblast fusion: lessons from flies and mice

News in fusion

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