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    Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism

    Fumagalli, M. and Camus, S.M. and Diekmann, Y. and Burke, A. and Camus, M.D. and Norman, P.J. and Joseph, A. and Abi-Rached, L. and Benazzo, A. and Rasteiro, R. and Mathieson, I. and Topf, Maya and Parham, P. and Thomas, M.G. and Brodsky, F.M. (2019) Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism. eLife 8 , e41517. ISSN 2050-084X.

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    Abstract

    CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding CLTCL1 gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogous CLTC gene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retaining CLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency CLTCL1 allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, altering its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22’s role in metabolism and have potential to differentially influence the human insulin response.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): Research Article, Cell Biology, Evolutionary Biology, evolutionary selection, membrane traffic, insulin response, Human
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    SWORD Depositor: Mr Joe Tenant
    Depositing User: Mr Joe Tenant
    Date Deposited: 20 Jun 2019 06:04
    Last Modified: 28 Jul 2019 23:59
    URI: http://eprints.bbk.ac.uk/id/eprint/27725

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