Invasive Podosomes and Myoblast Fusion

Chen, Elizabeth H.

doi:10.1016/b978-0-12-385891-7.00010-6

Cited by 41 publications

(47 citation statements)

References 76 publications

(167 reference statements)

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“…We demonstrate that PI(4,5)P2 enrichment is not asymmetric, suggesting that PI(4,5)P2 signaling functions on both sides of the fusion interface. These data agree with the requirement for Arp2/3 activity in both fusion partners (Abmayr and Pavlath, 2012;Chen, 2011). It will be interesting to address the function of PI(4,5)P2 on the myotube side in the future.…”

Section: Discussionsupporting

confidence: 84%

“…Engagement of these receptors prompts bidirectional signaling, resulting in the invasion of the FCM into the FC/myotube. Invasion is mediated by a podosome-like structure (PLS) within the established fusogenic synapse (Abmayr and Pavlath, 2012;Chen, 2011). The PLS is dependent on the Arp2/3 regulators Scar (also known as Wave) and WASp.…”

Section: Introductionmentioning

confidence: 99%

“…Together, these data suggested that PI(3,4,5)P3 is not associated with fusion under these conditions. PI(4,5)P2 is enriched at the fusion interface of both FCs/ myotubes and FCMs Myoblast fusion is an asymmetric process in which single FCMs actively and irreversibly invade and fuse with the growing FC/ myotube (Abmayr and Pavlath, 2012;Chen, 2011). On the subcellular level, this asymmetry manifests in the uneven distribution of F-actin.…”

Section: Introductionmentioning

confidence: 99%

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PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site

2014

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Cell-cell fusion is a regulated process that requires merging of the opposing membranes and underlying cytoskeletons. However, the integration between membrane and cytoskeleton signaling during fusion is not known. Using Drosophila, we demonstrate that the membrane phosphoinositide PI(4,5)P2 is a crucial regulator of F-actin dynamics during myoblast fusion. PI(4,5)P2 is locally enriched and colocalizes spatially and temporally with the F-actin focus that defines the fusion site. PI(4,5)P2 enrichment depends on receptor engagement but is upstream or parallel to actin remodeling. Regulators of actin branching via Arp2/3 colocalize with PI(4,5)P2 in vivo and bind PI(4,5)P2 in vitro. Manipulation of PI(4,5)P2 availability leads to impaired fusion, with a reduction in the F-actin focus size and altered focus morphology. Mechanistically, the changes in the actin focus are due to a failure in the enrichment of actin regulators at the fusion site. Moreover, improper localization of these regulators hinders expansion of the fusion interface. Thus, PI(4,5)P2 enrichment at the fusion site encodes spatial and temporal information that regulates fusion progression through the localization of activators of actin polymerization.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site

2014

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“…It is now clear that the foci are not symmetrically distributed between fusing partners but, instead, are very highly enriched in and possibly exclusive to the FCMs (Sens et al, 2010;Haralalka et al, 2011) (Figs 5, 7). These foci are part of a protrusive structure that pushes from the FCM into the developing founder cell or myotube, suggesting that fusion is a highly asymmetric event driven molecularly and morphologically in the FCMs (Sens et al, 2010;Chen, 2011;Haralalka et al, 2011;Sung and Weaver, 2011).…”

Section: Reviewmentioning

confidence: 99%

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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“…The above-mentioned models have been utilized to clarify key molecules involved in trophoblast syncytialization. Apart from placental development, cell fusion is also a developmental program and is an essential process in many other systems and events, including fertilization, fusion in leech [15] and Chlamydomonas gametes [16], hyphal fusion in filamentous fungi [17], hypodermal cell fusions in the Caenorhabditis elegans hermaphrodite [18], myoblast fusion [19], and the formation of osteoclasts from monocytes [20][21][22][23]. Using live-cell imaging combined with other strategies, many interesting structures or molecules related to cell-cell fusion have been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Live Cell Imaging of In Vitro Human Trophoblast Syncytialization1

Wang

Dang

Zheng

et al. 2014

Biology of Reproduction

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Human trophoblast syncytialization, a process of cell-cell fusion, is one of the most important yet least understood events during placental development. Investigating the fusion process in a placenta in vivo is very challenging given the complexity of this process. Application of primary cultured cytotrophoblast cells isolated from term placentas and BeWo cells derived from human choriocarcinoma formulates a biphasic strategy to achieve the mechanism of trophoblast cell fusion, as the former can spontaneously fuse to form the multinucleated syncytium and the latter is capable of fusing under the treatment of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live-cell imaging manner. In this study, a live-cell imaging system was used to delineate the fusion process of primary term cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342 or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on the cell membranes of fusion partners before fusion and the exchange of cytoplasmic contents during fusion. In summary, this study provides the first video recording of the process of trophoblast syncytialization. Furthermore, the various live-cell imaging systems used in this study will help to yield molecular insights into the syncytialization process during placental development.

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Invasive Podosomes and Myoblast Fusion

Cited by 41 publications

References 76 publications

PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site

PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site

Myoblast fusion: lessons from flies and mice

Live Cell Imaging of In Vitro Human Trophoblast Syncytialization1

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