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    Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography

    Atherton, Joe and Stouffer, M. and Francis, F. and Moores, Carolyn A. (2022) Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. Journal of Cell Science 135 (7), ISSN 0021-9533. (In Press)

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    Abstract

    Neurons extend axons to form the complex circuitry of the mature brain. This depends on the coordinated response and continuous remodelling of the microtubule and F-actin networks in the axonal growth cone. Growth cone architecture remains poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron growth cones using cryo-electron tomography to directly visualise their threedimensional subcellular architecture with molecular detail. Our data show the hexagonal arrays of actin bundles that form filopodia penetrate and terminate deep in the growth cone interior. We directly observe the modulation of these and other growth cone actin bundles by alteration of individual F-actin helical structures. Microtubules with blunt, slightly flared, or gently curved ends predominate in the growth cone, frequently contain lumenal particles and carry lattice defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental cytoskeleton regulator, on growth cone cytoskeleton shows no major anomalies in overall growth cone organisation or in F-actin subpopulations. However, our data suggest that microtubules sustain more structural defects, highlighting the importance of microtubule integrity during growth cone migration.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): neuron, growth cone, cytoskeleton, actin, microtubule, doublecortin
    School: School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 08 Apr 2022 13:29
    Last Modified: 10 Apr 2022 03:54
    URI: https://eprints.bbk.ac.uk/id/eprint/47995

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