The actin cytoskeleton provides mechanical support for cells and generates forces to drive cell shape changes and cell migration in morphogenesis. Molecular understanding of actin dynamics requires a genetically traceable model system that allows interdisciplinary experimental approaches to elucidate the regulatory network of cytoskeletal proteins in vivo. Here, we will discuss some examples of how advances in Drosophila genetics and high-resolution imaging techniques contribute to the discovery of new actin functions, signaling pathways, and mechanisms of actin regulation in vivo.
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http://dx.doi.org/10.1007/164_2016_33 | DOI Listing |
iScience
January 2025
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
Cancers and neurodegenerative disorders are associated with both disrupted proteostasis and altered nuclear morphology. Determining if changes in nuclear morphology contribute to pathology requires an understanding of the underlying mechanisms, which are difficult to elucidate in cells where pleiotropic effects of altering proteostasis might indirectly influence nuclear morphology. To investigate direct effects, we studied nuclei assembled in egg extract where potentially confounding effects of transcription, translation, cell cycle progression, and actin dynamics are absent.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Division of Hemostasis and Thrombosis, Department of Medicine, BIDMC, Harvard Medical School, Boston, MA, USA.
The actin cytoskeleton serves an important, but poorly characterized, role in controlling granule exocytosis. The dynamic nature of actin remodeling allows it to act both as a barrier to prevent indiscriminate granule release and as a facilitator of membrane fusion. In its capacity to promote exocytosis, filamentous actin binds to components of the exocytotic machinery through actin binding proteins, but also through direct interactions with SNAREs.
View Article and Find Full Text PDFDiabetic kidney disease (DKD) progression is often marked by early glomerular endothelial cell (GEC) dysfunction, including alterations in the fenestration size and number linked to impaired glomerular filtration. However, the cellular mechanisms regulating GEC fenestrations remain poorly understood due to limitations in existing models, challenges in imaging small fenestrations , and inconsistencies between and findings. This study used a logic-based protein-protein interaction network model with normalized Hill functions for dynamics to explore how glucose-mediated signaling dysregulation impacts fenestration dynamics in GECs.
View Article and Find Full Text PDFStem cells adapt to their local mechanical environment by rearranging their cytoskeleton, which underpins the evolution of their shape and fate as well as the emergence of tissue structure and function. Here, in the second part of a two-part experimental series, we aimed to elucidate spatiotemporal cytoskeletal remodeling and resulting changes in morphology and mechanical properties of cells and their nuclei. Akin to mechanical testing of the most basic living and adapting unit of life, i.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Department of Computer and Information Sciences, Department of Materials Science and Engineering, University of Delaware, Newark, Delaware 19716, United States.
Liquid phase-separating proteins can form condensates that play an important role in spatial and temporal organization of biological cells. The understanding of the mechanisms that lead to the formation of protein condensates and their interactions with other biomolecules may lead to processing routes for soft materials with tailored geometry and function. Fused in sarcoma (FUS) is an example of a nuclear protein that forms stable complexes, and recent studies have highlighted its ability to wet actin filaments and bundle them into networks.
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