For years, scientists have been trying to understand how molecular motors, which “drive” the filaments, are able to move the cellular cargo along the cytoskeleton. However, the organization and regulation of these filamentous structures themselves have not been well understood.
Scientists at the National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health, and their collaborators discovered that the cytoskeleton is not a static, unmoving structure, as was widely believed. Instead, the cytoskeleton undergoes dynamic changes that allow the cell to adjust to its ever-changing environment. The researchers also discovered that a complex of molecules called the actomyosin cortex (AC) initiates the mechanical changes that drive cytoskeleton rearrangement and cell movement.
“Cytoskeletal filaments undergo dynamic changes, driven by the AC, that control cell shape, movement, and division,” said principal investigator Dr. Franck Perez. “This discovery changes the traditional way scientists have viewed the cytoskeleton and has implications for understanding cell migration and how the cytoskeleton contributes to human disease.”
The research team used state-of-the-art imaging to examine live, three-dimensional zebrafish embryos to uncover the dynamic nature of the cytoskeleton and the function of the AC. The researchers report their findings in the journal Developmental Cell .
The NICHD team chose to examine the cytoskeleton of zebrafish embryos because the cells undergo rapid and extensive movements during development. They focused on the AC, a network of bundled actin filaments and myosin motor proteins located underneath the cell membrane. The AC contracts to mechanically drive cell shape changes. Using advanced microscopy techniques, the team imaged zebrafish embryos expressing genetically encoded fluorescent tags that specifically bind to the AC.
The team found that the cytoskeleton and AC are interconnected and act as one “unified cytoskeleton.” The AC controls cellular tension, which drives cytoskeleton rearrangement and cell movement. These findings provide a new framework for understanding how cells achieve directed movements and undergo shape changes.
“The cytoskeleton is not only responsible for cell movement, but also drives tissue-level movements and organ development during embryogenesis,” said Dr. Perez. “Dysregulated cytoskeletal dynamics contribute to neurodevelopmental diseases, as well as cancer and other human disorders, underscoring the potential clinical implications of our findings.”
