In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans

被引:69
作者
Kwiatkowski, Adam V. [1 ]
Maiden, Stephanie L. [2 ,3 ]
Pokutta, Sabine [4 ]
Choi, Hee-Jung [4 ]
Benjamin, Jacqueline M. [1 ]
Lynch, Allison M. [5 ]
Nelson, W. James [1 ,6 ]
Weis, William I. [4 ,6 ]
Hardin, Jeff [2 ,3 ]
机构
[1] Stanford Univ, Dept Biol, Stanford, CA 94305 USA
[2] Univ Wisconsin, Mol & Cellular Pharmacol Program, Madison, WI 53706 USA
[3] Univ Wisconsin, Dept Zool, Madison, WI 53706 USA
[4] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA
[5] Univ Wisconsin, Genet Program, Madison, WI 53706 USA
[6] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA
基金
美国国家卫生研究院;
关键词
cell-cell adhesion; HMP-1; HMP-2; HMR-1; CELL-CELL ADHESION; ALPHA-CATENIN; CRYSTAL-STRUCTURE; BETA-CATENIN; F-ACTIN; INTRAMOLECULAR ASSOCIATION; ADHERENS JUNCTIONS; TAIL DOMAINS; VINCULIN; BINDING;
D O I
10.1073/pnas.1007349107
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
The ternary complex of cadherin, beta-catenin, and alpha-catenin regulates actin-dependent cell-cell adhesion. alpha-Catenin can bind beta-catenin and F-actin, but in mammals alpha-catenin either binds beta-catenin as a monomer or F-actin as a homodimer. It is not known if this conformational regulation of alpha-catenin is evolutionarily conserved. The Caenorhabditis elegans alpha-catenin homolog HMP-1 is essential for actin-dependent epidermal enclosure and embryo elongation. Here we show that HMP-1 is a monomer with a functional C-terminal F-actin binding domain. However, neither full-length HMP-1 nor a ternary complex ofHMP-1-HMP-2(beta-catenin)-HMR-1(cadherin)bind F-actin in vitro, suggesting that HMP-1 is auto-inhibited. Truncation of either the F-actin or HMP-2 binding domain of HMP-1 disrupts C. elegans development, indicating that HMP-1 must be able to bind F-actin and HMP-2 to function in vivo. Our study defines evolutionarily conserved properties of alpha-catenin and suggests that multiple mechanisms regulate alpha-catenin binding to F-actin.
引用
收藏
页码:14591 / 14596
页数:6
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