Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons

Qi, Yanmei; Andolfi, Laura; Frattini, Flavia; Mayer, Florian; Lazzarino, Marco; Hu, Jing

doi:10.1038/ncomms9512

Cited by 136 publications

(147 citation statements)

References 55 publications

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“…This differs from previously identified Piezo1 regulatory proteins including polycystein-2 (PC-2) and stomatin-like protein-3 (STOML3), which appears to regulate Piezo function through indirectly altering the membrane curvature or stiffness [34][35][36] . We thus went on to test how SERCA2 interaction could regulate Piezo1.…”

Section: Identification Of Sercas As Interacting Proteins Of Piezo1contrasting

confidence: 90%

A Protein Interaction Mechanism for Suppressing the Mechanosensitive Piezo Channels

Chi¹

2018

Biophysical Journal

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Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmicreticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residueconstituted intracellular linker connecting the pore-module and mechanotransductionmodule. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels.

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Section: Identification Of Sercas As Interacting Proteins Of Piezo1contrasting

confidence: 90%

A Protein Interaction Mechanism for Suppressing the Mechanosensitive Piezo Channels

Chi¹

2018

Biophysical Journal

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“…Whether the low-threshold regime depends on specific interactions between the channel and the ECM protein, or reflects more efficient stretching of the membrane mediated by adhesion of a “sticky” cantilever to the cell surface remains to be determined. Taken together, the results from the studies by Poole et al [50], Qi et al [51], and Gaub and Miller [52] suggest that the response of Piezo1 to outside-in mechanical forces can be modulated by cytoskeletal tethers and scaffold proteins.…”

Section: Effects Of the Cytoskeleton On Piezo1 Activationmentioning

confidence: 86%

“…Currents were observed with ~10nm pillar deflection, as compared to 100–1000nm deflections in the absence of STOML3. Subsequently, Qi et al showed that STOML3-mediated sensitization of Piezo1 depends on cholesterol binding, and proposed that STOML3 influences membrane mechanics and facilitates force transfer to the channel protein [51]. …”

Section: Effects Of the Cytoskeleton On Piezo1 Activationmentioning

confidence: 99%

How cells channel their stress: Interplay between Piezo1 and the cytoskeleton

Nourse

Pathak

2017

Seminars in Cell & Developmental Biology

183

160

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Cells constantly encounter mechanical stimuli in their environment, such as dynamic forces and mechanical features of the extracellular matrix. These mechanical cues are transduced into biochemical signals, and integrated with genetic and chemical signals to modulate diverse physiological processes. Cells also actively generate forces to internally transport cargo, to explore the physical properties of their environment and to spatially position themselves and other cells during development. Mechanical forces are therefore central to development, homeostasis, and repair. Several molecular and biophysical strategies are utilized by cells for detecting and generating mechanical forces. Here we discuss an important class of molecules involved in sensing and transducing mechanical forces – mechanically-activated ion channels. We focus primarily on the Piezo1 ion channel, and examine its relationship with the cellular cytoskeleton.

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“…It is easily imaginable that mechanically-activated channels like Piezo could be affected by the surrounding membrane properties. Their activity have already been shown to be highly dependent on the membrane stiffening [58] and thus the membrane chol content, but also on the level of fatty acid saturation [59]. Moreover, new insights in Piezo1 structure evidenced a bend in its transmembrane section [60], whose stabilization energy might be partly compensated by the surrounding lipids.…”

Section: Lipid Domains As Modulators Of Piezo1 and Pmca Membrane Locamentioning

confidence: 99%

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Conrard

Stommen

Cloos

et al. 2018

Cell Physiol Biochem

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Background/Aims: Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. Methods: Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. Results: Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. Conclusion: Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. Whether this results from lipid domain biophysical properties, the strength of their anchorage to the underlying cytoskeleton and/or their correspondence with inner plasma membrane leaflet lipids remains to be demonstrated.

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Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons

Cited by 136 publications

References 55 publications

A Protein Interaction Mechanism for Suppressing the Mechanosensitive Piezo Channels

A Protein Interaction Mechanism for Suppressing the Mechanosensitive Piezo Channels

How cells channel their stress: Interplay between Piezo1 and the cytoskeleton

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

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