Extracellular annexins and dynamin are important for sequential steps in myoblast fusion

and 3 Laboratory of Cellular and Molecular Biophysics, Program of Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
The Journal of Cell Biology (Impact Factor: 9.83). 12/2012; 200(1). DOI: 10.1083/jcb.201207012
Source: PubMed


Myoblast fusion into multinucleated myotubes is a crucial step in skeletal muscle development and regeneration. Here, we accumulated murine myoblasts at the ready-to-fuse stage by blocking formation of early fusion intermediates with lysophosphatidylcholine. Lifting the block allowed us to explore a largely synchronized fusion. We found that initial merger of two cell membranes detected as lipid mixing involved extracellular annexins A1 and A5 acting in a functionally redundant manner. Subsequent stages of myoblast fusion depended on dynamin activity, phosphatidylinositol(4,5)bisphosphate content, and cell metabolism. Uncoupling fusion from preceding stages of myogenesis will help in the analysis of the interplay between protein machines that initiate and complete cell unification and in the identification of additional protein players controlling different fusion stages.

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Available from: Santosh K Verma, Nov 10, 2014
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    • "Taken together, these findings indicate a pleiotropic role of dynamin in membrane fusion. Although dynamin does not promote membrane fusion by itself, it seems to act after a hemifusion state, facilitating the expansion of the fusion pore (71). The underlying mechanism probably relies on dynamin ability to sense membrane curvature and remodel membranes (91). "
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    ABSTRACT: Dynamin-2 is a ubiquitously expressed mechano-GTPase involved in different stages of the secretory pathway. Its most well-known function relates to the scission of nascent vesicles from the plasma membrane during endocytosis; however, it also participates in the formation of new vesicles from the Golgi network, vesicle trafficking, fusion processes and in the regulation of microtubule, and actin cytoskeleton dynamics. Over the last 8 years, more than 20 mutations in the dynamin-2 gene have been associated to two hereditary neuromuscular disorders: Charcot-Marie-Tooth neuropathy and centronuclear myopathy. Most of these mutations are grouped in the pleckstrin homology domain; however, there are no common mutations associated with both disorders, suggesting that they differently impact on dynamin-2 function in diverse tissues. In this review, we discuss the impact of these disease-related mutations on dynamin-2 function during vesicle trafficking and endocytotic processes.
    Frontiers in Endocrinology 09/2013; 4:126. DOI:10.3389/fendo.2013.00126
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    • "As we discuss below, all three dynamin isoforms are expressed in the nervous system, where their most well-described role is in membrane fission during clathrin-mediated-endocytosis (CME) of synaptic vesicle membranes and membrane proteins. In addition to its role in CME, dynamin functions have been extended to other cellular processes such as caveolin-dependent internalization (Henley et al. 1998), vesicle budding from Golgi membranes (Jones et al. 1998) and endosomes (Nicoziani et al. 2000), regulation of microtubule stability (Thompson et al. 2004), actin cytoskeleton dynamics (Mooren et al. 2009; Gu et al. 2010), and fusion processes (De la Vega et al. 2011; Reid et al. 2012; Leikina et al. 2013). Whether each dynamin isoform specializes in a specific cellular function, or whether they exert overlapping roles in the nervous system is still unclear, as evidence arguing in favor of redundant (Raimondi et al. 2011) as well as differential roles of the three isoforms (Liu et al. 2011a) have Received July 31, 2013; revised manuscript received September 4, 2013; accepted September 12, 2013. "
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    ABSTRACT: Dynamin-2 is a pleiotropic GTPase whose best-known function is related to membrane scission during vesicle budding from the plasma or Golgi membranes. In the nervous system, dynamin-2 participates in synaptic vesicle recycling, postsynaptic receptor internalization, neurosecretion and neuronal process extension. Some of these functions are shared with the other two dynamin isoforms. However, the involvement of dynamin-2 in neurological illnesses points to a critical function of this isoform in the nervous system. In this regard, mutations in the dynamin-2 gene results in two congenital neuromuscular disorders. One of them, Charcot-Marie-Tooth disease, affects myelination and peripheral nerve conduction; whereas the other, Centronuclear Myopathy, is characterized by a progressive and generalized atrophy of skeletal muscles, yet it is also associated with abnormalities in the nervous system. Further, single nucleotide polymorphisms located in the dynamin-2 gene have been associated with sporadic Alzheimer Disease. In the present review, we discuss the pathogenic mechanisms implicated in these neurological disorders. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 09/2013; 128(2). DOI:10.1111/jnc.12455 · 4.28 Impact Factor
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    The Journal of Cell Biology 01/2012; 200(1):3-3. DOI:10.1083/jcb.2001if · 9.83 Impact Factor
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