Distinct mechanisms regulating mechanical force-induced Ca2+ signals at the plasma membrane and the ER in human MSCs

Kim, Tae Jin; Joo, Chirlmin; Seong, Jihye; Vafabakhsh, Reza; Botvinick, Elliot L.; Berns, Michael W.; Palmer, Amy E.; Wang, Ning; Ha, Taekjip; Jakobsson, Eric; Sun, Jie; Wang, Yingxiao

doi:10.7554/elife.04876

Cited by 86 publications

(105 citation statements)

References 79 publications

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“…[38] This suggests that the integrin-FAK complex might be connected with TRPM7 at DRM microdomain via cytoskeleton (CSK)-actomyosin network to regulate Ca 2+ signals. [41] Using this siRNA method, we observed that TRPM7 knockdown significantly inhibited the rigidity-dependent Ca 2+ mobilization at the DRM region, with nontargeting (NT) siRNA (control group) having minimal effects (n = 5-9, ***P < 0.001) (Figure 4e,f and Figure S6, Supporting Information). For example, TRPM7 regulates focal adhesions by controlling m-calpain, [39] and the inhibition of TRPM7 disrupts the actin cytoskeleton, and the focal assembly of myosin IIA and vinculin, a focal adhesion protein.…”

Section: Trpm7 Contributes To Ca 2+ Mobilization At Drm Regionmentioning

confidence: 93%

Matrix Rigidity‐Dependent Regulation of Ca²⁺ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

et al. 2018

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The dynamic regulation of signal transduction at plasma membrane microdomains remains poorly understood due to limitations in current experimental approaches. Genetically encoded biosensors based on fluorescent resonance energy transfer (FRET) can provide high spatiotemporal resolution for imaging cell signaling networks. Here, distinctive regulation of focal adhesion kinase (FAK) and Ca 2+ signals are visualized at different membrane microdomains by FRET using membrane‐targeting biosensors. It is shown that rigidity‐dependent FAK and Ca 2+ signals in human mesenchymal stem cells (hMSCs) are selectively activated at detergent‐resistant membrane (DRM or rafts) microdomains during the cell–matrix adhesion process, with minimal activities at non‐DRM domains. The rigidity‐dependent Ca 2+ signal at the DRM microdomains is downregulated by either FAK inhibition or lipid raft disruption, suggesting that FAK and lipid raft integrity mediate the in situ Ca 2+ activation. It is further revealed that transient receptor potential subfamily M7 (TRPM7) participates in the mobilization of Ca 2+ signals within DRM regions. Thus, the findings provide insights into the underlying mechanisms that regulate Ca 2+ and FAK signals in hMSCs under different mechanical microenvironments.

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Section: Trpm7 Contributes To Ca 2+ Mobilization At Drm Regionmentioning

confidence: 93%

Matrix Rigidity‐Dependent Regulation of Ca²⁺ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

et al. 2018

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“…Furthermore, subcellular structures influence the transmission of mechanical forces to cells. For instance, the cell cytoskeleton and its associated molecules relay this mechanical information to locations within the cell containing mechanosensitive proteins, such as the nucleus or the ER [94]. Thus, the cytoskeleton of osteocytes likely plays a critical role in flow-induced mechanosensing [95][96][97].…”

Section: Single-cell Studies To Probe Subcellular Mechanosensation Inmentioning

confidence: 99%

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems

Brown¹,

Sattler²

2016

Interface Focus.

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Despite advancements in technology and science over the last century, the mechanisms underlying Wolff's law—bone structure adaptation in response to physical stimuli—remain poorly understood, limiting the ability to effectively treat and prevent skeletal diseases. A challenge to overcome in the study of the underlying mechanisms of this principle is the multiscale nature of mechanoadaptation. While there exist in silico systems that are capable of studying across these scales, experimental studies are typically limited to interpretation at a single dimension or time point. For instance, studies of single-cell responses to defined physical stimuli offer only a limited prediction of the whole bone response, while overlapping pathways or compensatory mechanisms complicate the ability to isolate critical targets in a whole animal model. Thus, there exists a need to develop experimental systems capable of bridging traditional experimental approaches and informing existing multiscale theoretical models. The purpose of this article is to review the process of mechanoadaptation and inherent challenges in studying its underlying mechanisms, discuss the limitations of traditional experimental systems in capturing the many facets of this process and highlight three multiscale experimental systems which bridge traditional approaches and cover relatively understudied time and length scales in bone adaptation.

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“…Mechanical stimulation has been found to trigger calcium release in human mesangial stem cells (28). In our study, we recorded calcium signals from the proliferating mesenchymal tissue, an environment that, during organogenesis, creates and is exposed to mechanical forces from surrounding proliferating cells.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney

et al. 2018

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The central role of calcium signaling during development of early vertebrates is well documented, but little is known about its role in mammalian embryogenesis. We have used immunofluorescence and time-lapse calcium imaging of cultured explanted embryonic rat kidneys to study the role of calcium signaling for branching morphogenesis. In mesenchymal cells, we recorded spontaneous calcium activity that was characterized by irregular calcium transients. The calcium signals were dependent on release of calcium from intracellular stores in the endoplasmic reticulum. Down-regulation of the calcium activity, both by blocking the sarco-endoplasmic reticulum Ca 2+ -ATPase and by chelating cytosolic calcium, resulted in retardation of branching morphogenesis and a reduced formation of primitive nephrons but had no effect on cell proliferation. We propose that spontaneous calcium activity contributes with a stochastic factor to the self-organizing process that controls branching morphogenesis, a major determinant of the ultimate number of nephrons in the kidney.—Fontana, J. M., Khodus, G. R., Unnersjö-Jess, D., Blom, H., Aperia, A., Brismar, H. Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney.

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Distinct mechanisms regulating mechanical force-induced Ca2+ signals at the plasma membrane and the ER in human MSCs

Cited by 86 publications

References 79 publications

Matrix Rigidity‐Dependent Regulation of Ca²⁺ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

Matrix Rigidity‐Dependent Regulation of Ca²⁺ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems

Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney

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Distinct mechanisms regulating mechanical force-induced Ca2+ signals at the plasma membrane and the ER in human MSCs

Cited by 86 publications

References 79 publications

Matrix Rigidity‐Dependent Regulation of Ca2+ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

Matrix Rigidity‐Dependent Regulation of Ca2+ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems

Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney

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Product

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Matrix Rigidity‐Dependent Regulation of Ca²⁺ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer

Matrix Rigidity‐Dependent Regulation of Ca²⁺ at Plasma Membrane Microdomains by FAK Visualized by Fluorescence Resonance Energy Transfer