Distinct mechanisms regulating mechanical force-induced Ca2+ signals at the plasma membrane and the ER in human MSCs
| Autor: | Ning Wang, Michael W. Berns, Elliot L. Botvinick, Tae-Jin Kim, Jie Sun, Chirlmin Joo, Jihye Seong, Eric Jakobsson, Reza Vafabakhsh, Yingxiao Wang, Taekjip Ha, Amy E. Palmer |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
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Intracellular Space Biosensing Techniques Endoplasmic Reticulum FRET biosensor Cell membrane Fluorescence Resonance Energy Transfer Biology (General) Cytoskeleton mesenchymal stem cell Calcium signaling 0303 health sciences calcium signals General Neuroscience 030302 biochemistry & molecular biology calcium signal Actomyosin General Medicine Biophysics and Structural Biology Cell biology medicine.anatomical_structure Medicine Mechanosensitive channels Intracellular Research Article QH301-705.5 Science Biology Transfection General Biochemistry Genetics and Molecular Biology Contractility 03 medical and health sciences optical laser tweezers Extracellular medicine Animals Humans Calcium Signaling mechanical stimulation 030304 developmental biology optical laser tweezer mesenchymal stem cells General Immunology and Microbiology Endoplasmic reticulum Cell Membrane molecular imaging Developmental Biology and Stem Cells Calcium Cattle Stress Mechanical |
| Zdroj: | eLife, Vol 4 (2015) eLife eLife, 4, 2015 |
| ISSN: | 2050-084X |
| Popis: | It is unclear that how subcellular organelles respond to external mechanical stimuli. Here, we investigated the molecular mechanisms by which mechanical force regulates Ca2+ signaling at endoplasmic reticulum (ER) in human mesenchymal stem cells. Without extracellular Ca2+, ER Ca2+ release is the source of intracellular Ca2+ oscillations induced by laser-tweezer-traction at the plasma membrane, providing a model to study how mechanical stimuli can be transmitted deep inside the cell body. This ER Ca2+ release upon mechanical stimulation is mediated not only by the mechanical support of cytoskeleton and actomyosin contractility, but also by mechanosensitive Ca2+ permeable channels on the plasma membrane, specifically TRPM7. However, Ca2+ influx at the plasma membrane via mechanosensitive Ca2+ permeable channels is only mediated by the passive cytoskeletal structure but not active actomyosin contractility. Thus, active actomyosin contractility is essential for the response of ER to the external mechanical stimuli, distinct from the mechanical regulation at the plasma membrane. DOI: http://dx.doi.org/10.7554/eLife.04876.001 eLife digest Cells receive many signals from their environment, for example, when they are compressed or pulled about by neighboring cells. Information about these ‘mechanical stimuli’ can be transmitted within the cell to trigger changes in gene expression and cell behavior. When a cell receives a mechanical stimulus, it can activate the release of calcium ions from storage compartments within the cell, including from a compartment called the endoplasmic reticulum. Calcium ions can also enter the cell from outside via channels located in the membrane that surrounds the cell (the plasma membrane). Kim et al. investigated how mechanical forces are transmitted in a type of human cell called mesenchymal stem cells using optical tweezers to apply a gentle force to the outside of a cell. These tweezers use a laser to attract tiny objects, in this case a bead attached to proteins in the cell's outer membrane. The cell's response to this mechanical stimulation was measured using a sensor protein that fluoresces a different color when it binds to calcium ions. With this set-up, Kim et al. found that mesenchymal stem cells are able to transmit mechanical forces to different depths within the cell. The forces can travel deep to trigger the release of calcium ions from the endoplasmic reticulum. This process involves a network of protein fibers that criss-cross to support the structure of a cell—called the cytoskeleton—and also requires proteins that are associated with the cytoskeleton to contract. However, calcium ion entry through the plasma membrane due to a mechanical force does not require these contractile proteins—only the cytoskeleton is involved. These results demonstrate that the transmission of mechanical signals to different depths within mesenchymal stem cells involves different components. Future work should shed light on how these mechanical signals control gene expression and the development of mesenchymal stem cells. DOI: http://dx.doi.org/10.7554/eLife.04876.002 |
| Databáze: | OpenAIRE |
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