TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells
Fred Gorelick, Michael H. Nathanson
Fred Gorelick, Michael H. Nathanson
Published April 13, 2020
Citation Information: J Clin Invest. 2020;130(5):2199-2201. https://doi.org/10.1172/JCI136525.
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Commentary

TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells

Abstract

Alterations in calcium signaling in pancreatic acinar cells can result in pancreatitis. Although pressure changes in the pancreas can elevate cytosolic calcium (Ca2+) levels, it is not known how transient pressure-activated elevations in calcium can cause prolonged calcium changes and consequent pancreatitis. In this issue of the JCI, Swain et al. describe roles for the mechanically activated plasma membrane calcium channels Piezo1 and transient receptor potential vanilloid subfamily 4 (TRPV4) in acinar cells. The authors used genetic deletion models and cell culture systems to investigate calcium signaling. Notably, activation of the Piezo1-dependent TRPV4 pathway was independent of the cholecystokinin (CCK) stimulation pathway. These results elegantly resolve an apparent discrepancy in calcium signaling and the pathogenesis of pancreatitis in pancreatic acinar cells.

Authors

Fred Gorelick, Michael H. Nathanson

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Figure 1

Model for membrane stretch activation of Piezo1/TRPV4 and calcium-signaling pathways.

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Model for membrane stretch activation of Piezo1/TRPV4 and calcium-signal...
(A) Following membrane deformity (e.g., stretch), Piezo1 is activated, causing a transient increase in cytosolic calcium as well as increased PLA2 activity. PLA metabolites then activate TRPV4, which opens to let calcium enter and ultimately depolarize the mitochondria (1). The two transporters can be activated by multiple stimuli. (B) Multiple calcium transporters can affect signaling and lead to mitochondrial depolarization and trigger inflammatory responses through NF-κB activation and mitochondrial injury. Whether RyRs are present at ER-mitochondrial contacts in acinar cells is unknown.