Cell migration is based on an actin treadmill, which in turn depends on recycling of G-actin across the cell, from the rear where F-actin disassembles, to the front, where F-actin polymerizes. To analyze the rates of the actin transport, we used the Virtual Cell software to solve the diffusion-drift-reaction equations for the G-actin concentration in a realistic three-dimensional geometry of the motile cell. Numerical solutions demonstrate that F-actin disassembly at the cell rear and assembly at the front, along with diffusion, establish a G-actin gradient that transports G-actin forward "globally" across the lamellipod. Alternatively, if the F-actin assembly and disassembly are distributed throughout the lamellipod, F-/G-actin turnover is local, and diffusion plays little role. Chemical reactions and/or convective flow of cytoplasm of plausible magnitude affect the transport very little. Spatial distribution of G-actin is smooth and not sensitive to F-actin density fluctuations. Finally, we conclude that the cell body volume slows characteristic diffusion-related relaxation time in motile cell from approximately 10 to approximately 100 s. We discuss biological implications of the local and global regimes of the G-actin transport.
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http://dx.doi.org/10.1529/biophysj.108.130096 | DOI Listing |
J Cell Biol
March 2025
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA.
While membrane proteins such as ion channels continuously turn over and require replacement, the mechanisms of specificity of efficient channel delivery to appropriate membrane subdomains remain poorly understood. GJA1-20k is a truncated Connexin43 (Cx43) isoform arising from translation initiating at an internal start codon within the same parent GJA1 mRNA and is requisite for full-length Cx43 trafficking to cell borders. GJA1-20k does not have a full transmembrane domain, and it is not known how GJA1-20k enables forward delivery of Cx43 hemichannels.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Laboratory of Cell Biology, Department of Orthopedic Surgery, University Hospital of Tübingen, Waldhörnlestraße 22, D-7207, Tübingen, Germany.
Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca ion channel, has been shown to be important in sensing mechanical stress, however its signal transduction pathway is not thoroughly understood.
View Article and Find Full Text PDFNat Immunol
January 2025
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia.
View Article and Find Full Text PDFNat Commun
November 2024
Department of Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Martinsried, Germany.
A key challenge for bottom-up synthetic biology is engineering a minimal module for self-division of synthetic cells. Actin-based cytokinetic rings are considered a promising structure to produce the forces required for the controlled excision of cell-like compartments such as giant unilamellar vesicles (GUVs). Despite prior demonstrations of actin ring targeting to GUV membranes and myosin-induced constriction, large-scale vesicle deformation has been precluded due to the lacking spatial control of these contractile structures.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
We have previously reported that the calcineurin inhibitor macrolide immunosuppressant Tacrolimus (TAC, FK506) can promote the migration and invasion of the human-derived extravillous trophoblast cells conducive to preventing implantation failure in immune-complicated gestations manifesting recurrent implantation failure. Although the exact mode of action of TAC in promoting implantation has yet to be elucidated, the integral association of its binding protein FKBP12 with the inositol triphosphate receptor (IP3R) regulated intracellular calcium [Ca]i channels in the endoplasmic reticulum (ER), suggesting that TAC can mediate its action through ER release of [Ca]i. Using the immortalized human-derived first-trimester extravillous trophoblast cells HTR8/SVneo, our data indicated that TAC can increase [Ca]I, as measured by fluorescent live-cell imaging using Fluo-4.
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