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Role of Piezo1 in cAMP‐Dependent Calcium Release From ER Stores in Endothelial Cells
Author(s) -
Santana Dianicha,
Malik Asrar B.,
Mehta Dolly,
Komarova Yulia A.
Publication year - 2019
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.2019.33.1_supplement.809.9
Subject(s) - piezo1 , mechanosensitive channels , mechanotransduction , endoplasmic reticulum , microbiology and biotechnology , calcium , stim1 , adenylyl cyclase , orai1 , chemistry , aequorin , calcium in biology , calcium signaling , biophysics , intracellular , ion channel , biology , signal transduction , biochemistry , receptor , organic chemistry
Endothelial cells (ECs) lining the vessel wall express various mechanosensing and mechanotransducing molecules that are responsible for converting mechanical cues into chemical signals to elicit specific cellular responses. The recently discovered mechanosensitive Ca 2+ channel Piezo1 plays an important role in sensing hydrostatic pressure and shear stress by ECs. However, specific mechanisms involved in Piezo1‐mediated mechanotransduction remains elusive. Using intracellular and endoplasmic reticulum (ER) calcium sensors to respectively monitor the changes in Ca 2+ I and Ca 2+ ER concentrations, we have shown that pharmacological activation of Piezo1 induces cAMP‐evoked Ca 2+ release from ER stores. Ca 2+ influx through Piezo1 leads to a transient activation of soluble adenylyl cyclase (sAC) which, in turn, activates cAMP‐dependent Ca 2+ release via Inositol TrisphosphateReceptor 2 (IP 3 R2), a calcium channel located in ER. Depletion of either sAC or IP 3 R2 markedly reduces the Piezo1‐mediated increase in cytosolic Ca 2+ I indicating that Ca 2+ ER release represents a positive feedback loop amplifying Ca 2+ signals in ECs. Our data, for the first time, demonstrate that mechanosensitive channels induces Ca 2+ release from the ER. Further work will establish the role of sAC and IP 3 R2 in regulating the adaptive cellular responses of ECs to mechanical cues. Support or Funding Information This work is supported by the National Institutes of Health T32HL007829 to DS and 2R01HL045638‐30 to ABM and YK. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .