Functional analyses of heteromeric human PIEZO1 Channels

被引：5
作者：
Gnanasambandam, Radhakrishnan [1 ]
Bee, Chilman [1 ,2 ]
Ziegler, Lynn [1 ]
Sachs, Frederick [1 ]
Gottlieb, Philip A. [1 ]
机构：
[1] SUNY Buffalo, Dept Physiol & Biophys, Buffalo, NY 14260 USA
[2] Univ Texas Med Branch, Dept Neurosci Cell Biol & Anat, Galveston, TX 77555 USA
来源：
PLOS ONE | 2018年 / 13卷 / 11期
基金：
美国国家卫生研究院;
关键词：
ION PERMEATION; MUTATIONS; KINETICS; MECHANOTRANSDUCTION; ARTHROGRYPOSIS; STOICHIOMETRY; CELL;
D O I：
10.1371/journal.pone.0207309
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
PIEZO1 and PIEZO2 are mechanosensitive channels (MSCs) important for cellular function and mutations in them lead to human disorders. We examined how functional heteromers form between subunits of PIEZO1 using the mutants E2117K, E2117D, and E2117A. Homomers of E2117K do not conduct. E2117A homomers have low conductance with rapid inactivation, and those of E2117D have high conductance with slow inactivation. Pairing E2117K with E2117D or E2117A with E2117D gave rise to new channel species representing heteromers with distinct conductances. Whole-cell currents from co-expression of E2117A and E2117D fit well with a linear-combination model of homomeric channel currents suggesting that functional channels do not form from freely-diffusing, randomly-mixed monomers in-vitro. Whole-cell current from coexpressed PIEZO1/PIEZO2 also fit as a linear combination of homomer currents. High-resolution optical images of fluorescently-tagged channels support this interpretation because coexpressed subunits segregate into discrete domains.
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页数：15
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