Filopodia are actin-rich structures, present on the surface of eukaryotic cells. These structures play a pivotal role by allowing cells to explore their environment, generate mechanical forces or perform chemical signaling. Their complex dynamics includes buckling, pulling, length and shape changes. We show that filopodia additionally explore their 3D extracellular space by combining growth and shrinking with axial twisting and buckling. Importantly, the actin core inside filopodia performs a twisting or spinning motion which is observed for a range of cell types spanning from earliest development to highly differentiated tissue cells. Non-equilibrium physical modeling of actin and myosin confirm that twist is an emergent phenomenon of active filaments confined in a narrow channel which is supported by measured traction forces and helical buckles that can be ascribed to accumulation of sufficient twist. These results lead us to conclude that activity induced twisting of the actin shaft is a general mechanism underlying fundamental functions of filopodia.
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http://dx.doi.org/10.1038/s41467-022-28961-x | DOI Listing |
Mol Biol Cell
December 2024
Department of Neuroscience, Jefferson Center for Synaptic Biology, Vickie and Jack Farber Institute for Neuroscience, Sydney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Development of neuronal connections is spatially and temporally controlled by extracellular cues which often activate their cognate cell surface receptors and elicit localized cellular responses. Here, we demonstrate the use of an optogenetic tool to activate receptor signaling locally to induce actin-mediated growth cone remodeling in neurons. Based on the light-induced interaction of light between Cryptochrome 2 (CRY2) and CIB1, we generated a bicistronic vector to co-expresses CRY2 fused to the intracellular domain of a guidance receptor and a membrane-anchored CIB1.
View Article and Find Full Text PDFThromb Haemost
December 2024
Division of Hematology, Faculty of Medicine, Excellence Center in Translational Hematology, Chulalongkorn University, Bangkok, Thailand.
Background: Megakaryocytes (MK) from Bernard-Soulier syndrome (BSS) induced pluripotent stem cells (iPSCs) yielded reduced numbers but increased sizes of platelets. The molecular mechanisms remain unclear. This study aims to determine roles of signaling molecules involved in this process.
View Article and Find Full Text PDFRes Sq
December 2024
Department of Biology, Indiana University, Indianapolis, IN.
Nat Cell Biol
November 2024
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Invasive membrane protrusions play a central role in a variety of cellular processes. Unlike filopodia, invasive protrusions are mechanically stiff and propelled by branched actin polymerization. However, how branched actin filaments are organized to create finger-like invasive protrusions is unclear.
View Article and Find Full Text PDFScience
August 2024
Sorbonne Université, INSERM, Institute of Myology, Centre of Research in Myology, UMRS 974, Paris, France.
Clathrin-mediated endocytosis has characteristic features in neuronal dendrites and presynapses, but how membrane proteins are internalized along the axon shaft remains unclear. We focused on clathrin-coated structures and endocytosis along the axon initial segment (AIS) and their relationship to the periodic actin-spectrin scaffold that lines the axonal plasma membrane. A combination of super-resolution microscopy and platinum-replica electron microscopy on cultured neurons revealed that AIS clathrin-coated pits form within "clearings", circular areas devoid of actin-spectrin mesh.
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