{alpha}-Catenin mediates initial E-cadherin-dependent cell-cell recognition and subsequent bond strengthening.
alpha-Catenin is essential in cadherin-mediated epithelium development and maintenance of tissues and in cancer progression and metastasis. However, recent studies question the conventional wisdom that alpha-catenin directly bridges the cadherin adhesion complex to the actin cytoskeleton. Therefore, whether alpha-catenin plays a direct role in cadherin-dependent cell adhesion is unknown. Here, single-molecule force spectroscopy measurements in cells depleted of alpha-catenin or expressing the hereditary diffuse gastric cancer associated V832M E-cadherin germ-line missense mutation show that alpha-catenin plays a critical role in cadherin-mediated intercellular recognition and subsequent multibond formation within the first 300 ms of cell contact. At short contact times, alpha-catenin mediates a 30% stronger interaction between apposing E-cadherin molecules than when it cannot bind the E-cadherin-beta-catenin complex. As contact time between cells increases, alpha-catenin is essential for the strengthening of the first intercellular cadherin bond and for the ensuing formation of additional bonds between the cells, all without the intervention of actin. These results suggest that a critical decision to form an adhesion complex between 2 cells occurs within an extremely short time span and at a single-molecule level and identify a previously unappreciated role for alpha-catenin in these processes.
Bajpai
Saumendra
S
Department of Chemical and Biomolecular Engineering, and Howard Hughes Medical Institute Graduate Training Program and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Correia
Joana
J
Feng
Yunfeng
Y
Figueiredo
Joana
J
Sun
Sean X
SX
Longmore
Gregory D
GD
Suriano
Gianpaolo
G
Wirtz
Denis
D
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D047468:Immunoprecipitation; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D012680:Sensitivity and Specificity; D014162:Transfection; D051178:alpha Catenin / Q000502:physiology*
D015820:Cadherins; D034741:RNA, Small Interfering; D051178:alpha Catenin