Tropomodulins: Pointed-end capping proteins that regulate actin filament architecture in diverse cell types

Sawako Yamashiro, David S. Gokhin, Sumiko Kimura, Roberta B. Nowak, Velia M. Fowler

    Research output: Contribution to journalArticlepeer-review

    77 Citations (Scopus)

    Abstract

    Tropomodulins are a family of four proteins (Tmods 1-4) that cap the pointed ends of actin filaments in actin cytoskeletal structures in a developmentally regulated and tissue-specific manner. Unique among capping proteins, Tmods also bind tropomyosins (TMs), which greatly enhance the actin filament pointed-end capping activity of Tmods. Tmods are defined by a TM-regulated/Pointed-End Actin Capping (TM-Cap) domain in their unstructured N-terminal portion, followed by a compact, folded Leucine-Rich Repeat/Pointed-End Actin Capping (LRR-Cap) domain. By inhibiting actin monomer association and dissociation from pointed ends, Tmods regulate actin dynamics and turnover, stabilizing actin filament lengths and cytoskeletal architecture. In this review, we summarize the genes, structural features, molecular and biochemical properties, actin regulatory mechanisms, expression patterns, and cell and tissue functions of Tmods. By understanding Tmods' functions in the context of their molecular structure, actin regulation, binding partners, and related variants (leiomodins 1-3), we can draw broad conclusions that can explain the diverse morphological and functional phenotypes that arise from Tmod perturbation experiments in vitro and in vivo. Tmod-based stabilization and organization of intracellular actin filament networks provide key insights into how the emergent properties of the actin cytoskeleton drive tissue morphogenesis and physiology.

    Original languageEnglish
    Pages (from-to)337-370
    Number of pages34
    JournalCytoskeleton
    Volume69
    Issue number6
    DOIs
    Publication statusPublished - 2012 Jun

    Keywords

    • Actin dynamics
    • Cell migration
    • Cell morphology
    • Membrane skeleton
    • Spectrin
    • Tropomyosin

    ASJC Scopus subject areas

    • Cell Biology
    • Structural Biology

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