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Piezo1 promotes ER Ca 2+ transport to regulate the cellular responses of endothelial cells to shear stress
Author(s) -
Santana Dianicha,
Komarova Asrar,
Mehta Dolly,
Komarova Yulia
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04362
Subject(s) - piezo1 , mechanotransduction , endoplasmic reticulum , unfolded protein response , microbiology and biotechnology , chemistry , mechanosensitive channels , biophysics , thapsigargin , biology , ion channel , biochemistry , receptor
Mechanotransduction is an essential mechanism by which endothelial cells (ECs) sense and adapt to the environment. Piezo1, a mechanosensitive cation channel, is responsible for sensing and transducing mechanical stimuli into chemical signals in endothelial cells. However, the signaling mechanism downstream of Piezo1 remains poorly understood. Here, we identified Piezo1‐mediated ER Ca 2+ transport as an essential element of endothelial cell adaptation to shear stress. Using the ER targeted calcium sensor G‐Cepia1er, we showed that both laminal fluid shear and pharmacological activation of Piezo1 induced Ca 2+ ER transport. Activation of Piezo1 led to rapid influx of Ca 2+ in the ER followed by Ca 2+ ER release via cAMP‐sensitized Inositol TrisphosphateReceptor 2 (IP 3 R2), a calcium channel located in the ER membrane. Inhibition of sarco/endoplasmic reticulum Ca 2+ ‐ATPase (SERCA) blocked Piezo1‐induced Ca 2+ entry in the ER but did not affect the rate of Ca 2+ ER release. In contrast, depletion of soluble Adenylyl Cyclase (sAC) markedly reduced the rate of Piezo1‐mediated Ca 2+ ER release without affecting Ca 2+ entry. These data indicate that the ER Ca 2+ transport induced by shear stress is finely regulated by Piezo1 downstream signaling. Furthermore, depletion of Piezo1, IP 3 R2 and sAC blocked alignment of ECs in the direction of shear flow. Our results provide evidence on how mechanical forces are transmitted to cellular organelles such as the ER and, for the first time, establish the role of Piezo1‐sAC‐IP 3 R2 mediated ER Ca 2+ transport as an essential signaling element of cell adaptation to mechanical cues.