共 72 条
A Weak Link with Actin Organizes Tight Junctions to Control Epithelial Permeability
被引:60
作者:

Belardi, Brian
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Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
Univ Calif Berkeley, Biophys Program, Berkeley, CA 94720 USA Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA

Hamkins-Indik, Tiama
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机构:
Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
Univ Calif Berkeley, Biophys Program, Berkeley, CA 94720 USA Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA

Harris, Andrew R.
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机构:
Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
Univ Calif Berkeley, Biophys Program, Berkeley, CA 94720 USA Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA

Kim, Jeongmin
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机构:
Seoul Natl Univ, Dept Transdisciplinary Studies, Seoul 08826, South Korea
Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA

Xu, Ke
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机构:
Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
Chan Zuckerberg Biohub, San Francisco, CA 94158 USA Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA

Fletcher, Daniel A.
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h-index: 0
机构:
Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
Univ Calif Berkeley, Biophys Program, Berkeley, CA 94720 USA
Chan Zuckerberg Biohub, San Francisco, CA 94158 USA
Lawrence Berkeley Natl Lab, Div Biol Syst & Engn, Berkeley, CA 94720 USA Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
机构:
[1] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Biophys Program, Berkeley, CA 94720 USA
[3] Seoul Natl Univ, Dept Transdisciplinary Studies, Seoul 08826, South Korea
[4] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[5] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA
[6] Lawrence Berkeley Natl Lab, Div Biol Syst & Engn, Berkeley, CA 94720 USA
关键词:
ADHERENS JUNCTIONS;
BINDING DOMAIN;
E-CADHERIN;
PHASE-SEPARATION;
CLAUDIN STRANDS;
ALPHA-CATENIN;
PROTEIN;
ZO-1;
ACTIVATION;
BARRIER;
D O I:
10.1016/j.devcel.2020.07.022
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
In vertebrates, epithelial permeability is regulated by the tight junction (TJ) formed by specialized adhesive membrane proteins, adaptor proteins, and the actin cytoskeleton. Despite the TJ's critical physiological role, a molecular-level understanding of how TJ assembly sets the permeability of epithelial tissue is lacking. Here, we identify a 28-amino-acid sequence in the TJ adaptor protein ZO-1, which is responsible for actin binding, and show that this interaction is essential for TJ permeability. In contrast to the strong interactions at the adherens junction, we find that the affinity between ZO-1 and actin is surprisingly weak, and we propose a model based on kinetic trapping to explain how affinity could affect TJ assembly. Finally, by tuning the affinity of ZO-1 to actin, we demonstrate that epithelial monolayers can be engineered with a spectrum of permeabilities, which points to a promising target for treating transport disorders and improving drug delivery.
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页码:792 / +
页数:20
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