Tropomodulin’s actin-binding abilities are required to modulate dendrite development

Kevin T. Gray*, Holly Stefen, Thu N. A. Ly, Christopher J. Keller, Mert Colpan, Gary A. Wayman, Edward Pate, Thomas Fath, Alla S. Kostyukova

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)
    39 Downloads (Pure)

    Abstract

    There are many unanswered questions about the roles of the actin pointed end capping and actin nucleation by tropomodulins (Tmod) in regulating neural morphology. Previous studies indicate that Tmod1 and Tmod2 regulate morphology of the dendritic arbor and spines. Tmod3, which is expressed in the brain, had only a minor influence on morphology. Although these studies established a defined role of Tmod in regulating dendritic and synaptic morphology, the mechanisms by which Tmods exert these effects are unknown. Here, we overexpressed a series of mutated forms of Tmod1 and Tmod2 with disrupted actin-binding sites in hippocampal neurons and found that Tmod1 and Tmod2 require both of their actin-binding sites to regulate dendritic morphology and dendritic spine shape. Proximity ligation assays (PLAs) indicate that these mutations impact the interaction of Tmod1 and Tmod2 with tropomyosins Tpm3.1 and Tpm3.2. This impact on Tmod/Tpm interaction may contribute to the morphological changes observed. Finally, we use molecular dynamics simulations (MDS) to characterize the structural changes, caused by mutations in the C-terminal helix of the leucine-rich repeat (LRR) domain of Tmod1 and Tmod2 alone and when bound onto actin monomers. Our results expand our understanding of how neurons utilize the different Tmod isoforms in development.

    Original languageEnglish
    Article number357
    Pages (from-to)1-12
    Number of pages12
    JournalFrontiers in Molecular Neuroscience
    Volume11
    DOIs
    Publication statusPublished - 9 Oct 2018

    Bibliographical note

    Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • Actin cytoskeleton
    • Actin dynamics
    • Hippocampal neuron culture
    • Neurite outgrowth
    • Tropomodulin

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