Focused Ultrasound Stimulates ER Localized Mechanosensitive PANNEXIN-1 to Mediate Intracellular Calcium Release in Invasive Cancer Cells

Lee, Nan Sook; Yoon, Chi Woo; Wang, Qing; Moon, San; Koo, Kweon Mo; Jung, Hayong; Chen, Ruimin; Jiang, Laiming; Lu, Guoxing; Fernandez, Antony; Chow, Robert H.; Weitz, Andrew C.; Salvaterra, Paul M.; Pinaud, Fabien; Shung, K. Kirk

doi:10.3389/fcell.2020.00504

Cited by 26 publications

(18 citation statements)

References 53 publications

(95 reference statements)

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“…The ER-localized PANX1 channel responded to ultrasound stimulations in invasive cancer cells causing the release of Ca 2+ from the ER (Figure 2). This response involved neither the cytoskeleton nor the PM PANX1 pool, thereby pointing toward a direct response by the ER pool of PANX1 (Lee et al, 2020). The Ca 2+ channel Piezo1, localized both at the PM and at the ER (McHugh et al, 2010;Gudipaty et al, 2017), was also found to respond to cell stretching from both locations (Nava et al, 2020).…”

Section: Endoplasmic Reticulummentioning

confidence: 87%

“…Despite these unique morphological features, only a few studies have investigated the relationship between mechanical cues and the ER. Nevertheless, recent evidence suggests that the ER harbors mechanosensitive and mechanotranducing elements (Nakayama et al, 2012;Kim et al, 2015;Lee et al, 2020;Nava et al, 2020).…”

Section: Endoplasmic Reticulummentioning

confidence: 99%

“…Mechanosensitive channels are present in the ER in fission yeast (Nakayama et al, 2012) and in mammalian cells (Lee et al, 2020). In fission yeast, hypo-osmotic shock-induced cell swelling activated Msy1 and Msy2, two proteins that localize to the perinuclear and the cortical ER, respectively.…”

Section: Endoplasmic Reticulummentioning

confidence: 99%

“…Recently, Lee et al (2020) demonstrated that PANX1 at the ER is also mechanosensory and functionally distinct from the PM localized PANX1. The ER-localized PANX1 channel responded to ultrasound stimulations in invasive cancer cells causing the release of Ca 2+ from the ER (Figure 2).…”

Section: Endoplasmic Reticulummentioning

confidence: 99%

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Endomembranes: Unsung Heroes of Mechanobiology?

Phuyal

Baschieri

2020

Front. Bioeng. Biotechnol.

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Mechanical stimuli have profound effects on the cellular architecture and functions. Over the past two decades, considerable progress has been made in unraveling the molecular machineries that confer cells the ability to sense and transduce mechanical input into biochemical signals. This has resulted in the identification of several forcesensing proteins or mechanically activated ion channels distributed throughout most cell types, whereby the plasma membrane, cytoskeleton, and the nucleus have garnered much attention. Although organelles from the endomembrane system make up significant portion of cell volume and play pivotal roles in the spatiotemporal distribution of signaling molecules, they have received surprisingly little attention in mechanobiology. In this mini-review, we summarize results that document participation of the endomembrane system in sensing and responding to mechanical cues.

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Section: Endoplasmic Reticulummentioning

confidence: 87%

Section: Endoplasmic Reticulummentioning

confidence: 99%

Section: Endoplasmic Reticulummentioning

confidence: 99%

Section: Endoplasmic Reticulummentioning

confidence: 99%

See 2 more Smart Citations

Endomembranes: Unsung Heroes of Mechanobiology?

Phuyal

Baschieri

2020

Front. Bioeng. Biotechnol.

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“…Further, PANX1 is activated when cancer cells are subjected to deformation as they travel along the microvasculature, which contributes to cancer metastasis [41]. Moreover, focused ultrasound (FUS) can stimulate ER-localized mechanosensitive PANX1 and result in the release of Ca 2+ from the ER in invasive cancer cells [42].…”

mentioning

confidence: 99%

Mechanisms of Pannexin 1 (PANX1) Channel Mechanosensitivity and Its Pathological Roles

Yang

Xiao

et al. 2022

IJMS

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Pannexins (PANX) were cloned based on their sequence homology to innexins (Inx), invertebrate gap junction proteins. Although there is no sequence homology between PANX and connexins (Cx), these proteins exhibit similar configurations. The PANX family has three members, PANX1, PANX2 and PANX3. Among them, PANX1 has been the most extensively studied. The PANX1 channels are activated by many factors, including high extracellular K+ ([K+]e), high intracellular Ca2+ ([Ca2+]i), Src family kinase (SFK)-mediated phosphorylation, caspase cleavage and mechanical stimuli. However, the mechanisms mediating this mechanosensitivity of PANX1 remain unknown. Both force-from-lipids and force-from-filaments models are proposed to explain the gating mechanisms of PANX1 channel mechanosensitivity. Finally, both the physiological and pathological roles of mechanosensitive PANX1 are discussed.

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Acoustofluidic Stimulation of Functional Immune Cells in a Microreactor

et al. 2022

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The cytotoxic response of natural killer (NK) cells in a microreactor to surface acoustic waves (SAWs) is investigated, where the SAWs produce an acoustic streaming flow. The Rayleigh-type SAWs form by an interdigital transducer propagated along the surface of a piezoelectric substrate in order to allow the dynamic stimulation of functional immune cells in a noncontact and rotor-free manner. The developed acoustofluidic microreactor enables a dynamic cell culture to be set up in a miniaturized system while maintaining the performance of agitating media. The present SAW system creates acoustic streaming flow in the cylindrical microreactor and applies flow-induced shear stress to the cells. The suspended NK cells are found to not be damaged by the SAW operation of the adjusted experimental setup. Suspended NK cell aggregates subjected to an SAW treatment show increased intracellular Ca 2+ concentrations. Simultaneously treating the NK cells with SAWs and protein kinase C activator enhances the lysosomal protein expressions of the cells and the cell-mediated cytotoxicity against target tumor cells. These have important implications by showing that acoustically actuated system allows dynamic cell culture without cell damages and further alters cytotoxicity-related cellular activities.

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Focused Ultrasound Stimulates ER Localized Mechanosensitive PANNEXIN-1 to Mediate Intracellular Calcium Release in Invasive Cancer Cells

Cited by 26 publications

References 53 publications

Endomembranes: Unsung Heroes of Mechanobiology?

Endomembranes: Unsung Heroes of Mechanobiology?

Mechanisms of Pannexin 1 (PANX1) Channel Mechanosensitivity and Its Pathological Roles

Acoustofluidic Stimulation of Functional Immune Cells in a Microreactor

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