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  • Halichoerus grypus  (1)
  • NF2  (1)
  • Nature Publishing Group  (2)
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  • Nature Publishing Group  (2)
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  • 1
    Publication Date: 2022-05-26
    Description: © Macmillan Publishers, 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Oncogene 32 (2013): 1135–1143, doi:10.1038/onc.2012.135.
    Description: Neurofibromatosis type 2 patients develop schwannomas, meningiomas and ependymomas resulting from mutations in the tumor suppressor gene, NF2, encoding a membrane-cytoskeleton adapter protein called merlin. Merlin regulates contact inhibition of growth and controls the availability of growth factor receptors at the cell surface. We tested if microtubule-based vesicular trafficking might be a mechanism by which merlin acts. We found that schwannoma cells, containing merlin mutations and constitutive activation of the Rho/Rac family of GTPases, had decreased intracellular vesicular trafficking relative to normal human Schwann cells. In Nf2−/− mouse Schwann (SC4) cells, re-expression of merlin as well as inhibition of Rac or its effector kinases, MLK and p38SAPK, each increased the velocity of Rab6 positive exocytic vesicles. Conversely, an activated Rac mutant decreased Rab6 vesicle velocity. Vesicle motility assays in isolated squid axoplasm further demonstrated that both mutant merlin and active Rac specifically reduce anterograde microtubule-based transport of vesicles dependent upon the activity of p38SAPK kinase. Taken together, our data suggest loss of merlin results in the Rac-dependent decrease of anterograde trafficking of exocytic vesicles, representing a possible mechanism controlling the concentration of growth factor receptors at the cell surface.
    Description: This work was supported by NIH R01 CA118032 (to NR), and MBL research fellowships (to NR and GM), NIH R01 NS23868 (to STB).
    Keywords: Merlin ; NF2 ; Rac ; Trafficking ; Exocytosis
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 2
    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Emerging Microbes and Infections 5 (2016): e81, doi:10.1038/emi.2016.77.
    Description: Influenza A virus (IAV) has been associated with multiple unusual mortality events (UMEs) in North Atlantic pinnipeds, frequently attributed to spillover of virus from wild-bird reservoirs. To determine if endemic infection persists outside of UMEs, we undertook a multiyear investigation of IAV in healthy, live-captured Northwest Atlantic gray seals (Halichoerus grypus). From 2013 to 2015, we sampled 345 pups and 57 adults from Cape Cod, MA, USA and Nova Scotia, Canada consistently detecting IAV infection across all groups. There was an overall viral prevalence of 9.0% (95% confidence interval (CI): 6.4%–12.5%) in weaned pups and 5.3% (CI: 1.2%–14.6%) in adults, with seroprevalences of 19.3% (CI: 15.0%–24.5%) and 50% (CI: 33.7%–66.4%), respectively. Positive sera showed a broad reactivity to diverse influenza subtypes. IAV status did not correlate with measures of animal health nor impact animal movement or foraging. This study demonstrated that Northwest Atlantic gray seals are both permissive to and tolerant of diverse IAV, possibly representing an endemically infected wild reservoir population.
    Description: This work was supported in part by National Institute of Allergy and Infectious Diseases (NIAID), the Centers of Excellence for Influenza Research and Surveillance (CEIRS) HHSN272201400008C, MIT Sea Grant Project 2013-DOH-45-LEV, National Science and Engineering Research Council of Canada (NSERC), NMFS #17670-01, NMFS #10080-95 and FWS #53514-13003.
    Keywords: Gray seal ; Halichoerus grypus ; Influenza ; Pinniped ; Reservoir ; Telemetry
    Repository Name: Woods Hole Open Access Server
    Type: Article
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