Profilin Directly Enhances Microtubule Growth Through Residues Mutated in Amyotrophic Lateral Sclerosis.

Jessica L. Henty-ridilla, M.Angeles Juanes, BL Goode

    Research output: Contribution to journalConference articlepeer-review

    Abstract

    Profilin is one of the most abundant and central actin regulatory proteins in eukaryotic cells. Profilin also
    decorates the sides of microtubules and indirectly influences cellular microtubule dynamics through
    interactions with Formins. Here, we investigated whether Profilin has direct regulatory effects on
    microtubule dynamics. We show that human Profilin‐1 binds to microtubules in vitro and enhances the
    growth rate of microtubules several‐fold. These microtubule effects are conserved in budding yeast and
    Drosophila Profilin homologs, and are unaffected by mutations in its canonical actin monomer– or poly‐
    L‐proline–binding sites. Instead, microtubule regulation depends on several residues mutated in patients
    with amyotrophic lateral sclerosis (ALS). The enhanced microtubule dynamics elicited by Profilin are
    attenuated by increasing concentrations of actin monomers. This suggests a competitive relationship
    between microtubules and actin for Profilin binding and this agrees with the close proximity of the
    known actin and microtubule binding surfaces. Consistent with these biochemical results, a two‐fold
    increase in expression of wildtype Profilin accelerates the growth rate of microtubules in cells, and cells
    expressing similar levels of each of the ALS‐associated Profilin mutants did not. These results
    demonstrate Profilin directly interacts with and enhances the growth rate of microtubules in vitro and in
    cells, and indicate that Profilin coordinates cellular actin and microtubule dynamics. Further, cells
    harboring ALS‐linked Profilin mutations may ultimately leads to the motor neuron degeneration through
    defective microtubule regulation.
    Original languageEnglish
    Pages (from-to)1138
    JournalMolecular Biology of the Cell
    Volume28
    Publication statusPublished - 2017
    Event2017 Annual Joint Meeting of the American Society for Cell Biology and the European Molecular Biology Organization - Philadelphia, United States
    Duration: 2 Dec 20176 Dec 2017

    Bibliographical note

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739290/

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