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Tytuł:
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A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel.
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Autorzy:
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Geng J; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Liu W; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Joint Graduate Program of Peking-Tsinghua-NIBS, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Zhou H; MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Zhang T; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Wang L; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Zhang M; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Li Y; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Shen B; MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Li X; MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: .
Xiao B; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China. Electronic address: .
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Źródło:
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Neuron [Neuron] 2020 May 06; Vol. 106 (3), pp. 438-451.e6. Date of Electronic Publication: 2020 Mar 05.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: [Cambridge, Mass. : Cell Press, c1988-
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MeSH Terms:
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Ion Channel Gating*
Ion Channels/*metabolism
Animals ; HEK293 Cells ; HeLa Cells ; Humans ; Ion Channels/chemistry ; Male ; Mechanotransduction, Cellular ; Mice ; Mice, Inbred C57BL ; Protein Isoforms/chemistry ; Protein Isoforms/metabolism
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Contributed Indexing:
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Keywords: Piezo1; Piezo2; gating; ion permeation; isoform; mechanosensitive ion channel; mechanotransduction; plug-and-latch
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Substance Nomenclature:
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0 (Ion Channels)
0 (PIEZO1 protein, human)
0 (PIEZO2 protein, human)
0 (Protein Isoforms)
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Entry Date(s):
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Date Created: 20200307 Date Completed: 20200824 Latest Revision: 20200824
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Update Code:
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20240105
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DOI:
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10.1016/j.neuron.2020.02.010
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PMID:
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32142647
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The mechanosensitive Piezo1 and Piezo2 channels convert mechanical force into cation permeation. However, their precise mechanogating and regulatory mechanisms remain elusive. Here, we report that Piezo1 utilizes three lateral ion-conducting portals equipped with physical gates for cooperative gating and splicing regulation. Mutating residues lining the portal converts Piezo1 into an anion-selective channel, demonstrating the portal-based cation-permeating pathway. Intriguingly, the portal is physically blocked with a plug domain, which undergoes alternative splicing in both Piezo1 and Piezo2. The Piezo1 isoform has local openings of the portals, enlarged single-channel conductance and sensitized mechanosensitivity. Remarkably, the three plugs are strategically latched onto the central axis for coordinated gating of the three portals. Disrupting the latching induces three quantal sub-conductance states in Piezo1, but not in the isoform. Together, we propose that Piezo utilizes an elegant plug-and-latch mechanism to physically and coordinately gate the lateral portals through the spliceable plug gates.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Comment in: Neuron. 2020 May 6;106(3):361-363. (PMID: 32380048)