Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2
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Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2. / Verkest, Clement; Schaefer, Irina; Nees, Timo A; Wang, Na; Jegelka, Juri M; Taberner, Francisco J; Lechner, Stefan G.
in: NAT COMMUN, Jahrgang 13, Nr. 1, 1365, 15.03.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2
AU - Verkest, Clement
AU - Schaefer, Irina
AU - Nees, Timo A
AU - Wang, Na
AU - Jegelka, Juri M
AU - Taberner, Francisco J
AU - Lechner, Stefan G
N1 - © 2022. The Author(s).
PY - 2022/3/15
Y1 - 2022/3/15
N2 - A central question in mechanobiology is how mechanical forces acting in or on cells are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we examined the role of the intracellular domains of PIEZO2, which account for 25% of the channel, and demonstrate that these domains fine-tune properties such as poking and stretch-sensitivity, velocity coding and single channel conductance. Moreover, we show that the intrinsically disordered linker between the transmembrane helices twelve and thirteen (IDR5) is required for the activation of PIEZO2 by cytoskeleton-transmitted forces. The deletion of IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, while it only partially affected its sensitivity to cell indentation and does not alter its stretch sensitivity. Thus, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO function.
AB - A central question in mechanobiology is how mechanical forces acting in or on cells are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we examined the role of the intracellular domains of PIEZO2, which account for 25% of the channel, and demonstrate that these domains fine-tune properties such as poking and stretch-sensitivity, velocity coding and single channel conductance. Moreover, we show that the intrinsically disordered linker between the transmembrane helices twelve and thirteen (IDR5) is required for the activation of PIEZO2 by cytoskeleton-transmitted forces. The deletion of IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, while it only partially affected its sensitivity to cell indentation and does not alter its stretch sensitivity. Thus, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO function.
KW - Cytoskeleton/metabolism
KW - Ion Channels/metabolism
KW - Mechanotransduction, Cellular/physiology
U2 - 10.1038/s41467-022-28974-6
DO - 10.1038/s41467-022-28974-6
M3 - SCORING: Journal article
C2 - 35292651
VL - 13
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
M1 - 1365
ER -