Rule-based modelling provides an extendable framework for comparing candidate mechanisms underpinning clathrin polymerisation View Full Text


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Article Info

DATE

2018-12

AUTHORS

Anatoly Sorokin, Katharina F. Heil, J. Douglas Armstrong, Oksana Sorokina

ABSTRACT

Polymerisation of clathrin is a key process that underlies clathrin-mediated endocytosis. Clathrin-coated vesicles are responsible for cell internalization of external substances required for normal homeostasis and life -sustaining activity. There are several hypotheses describing formation of closed clathrin structures. According to one of the proposed mechanisms cage formation may start from a flat lattice buildup on the cellular membrane, which is later transformed into a curved structure. Creation of the curved surface requires rearrangement of the lattice, induced by additional molecular mechanisms. Different potential mechanisms require a modeling framework that can be easily modified to compare between them. We created an extendable rule-based model that describes polymerisation of clathrin molecules and various scenarios of cage formation. Using Global Sensitivity Analysis (GSA) we obtained parameter sets describing clathrin pentagon closure and the emergence/production and closure of large-size clathrin cages/vesicles. We were able to demonstrate that the model can reproduce budding of the clathrin cage from an initial flat array. More... »

PAGES

5658

References to SciGraph publications

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  • 2004-12. Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating in NATURE
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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-23829-x

    DOI

    http://dx.doi.org/10.1038/s41598-018-23829-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101862144

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29618727


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