Cadherin controls nectin recruitment into adherens junctions by remodeling the actin cytoskeleton.
The mechanism that coordinates activities of different adhesion receptors is poorly understood. We investigated this mechanism by focusing on the nectin-2 and E-cadherin adherens junction receptors. We found that, cadherin was not required for the basic process of nectin junction formation because nectin-2 formed junctions in cadherin-deficient A431D cells. Formation of nectin-2 junctions in these cells, however, became regulated by cadherin as soon as E-cadherin was re-expressed. E-cadherin recruited nectin-2 into adherens junctions, where both proteins formed distinct but tightly associated clusters. Live-cell imaging showed that the appearance of E-cadherin clusters often preceded that of nectin-2 clusters at sites of junction assembly. Inactivation of E-cadherin clustering by different strategies concomitantly suppressed the formation of nectin clusters. Furthermore, cadherin significantly increased the stability of nectin clusters, thereby making them resistant to the BC-12 antibody, which targets the nectin-2 adhesion interface. By testing different E-cadherin-α-catenin chimeras, we showed that the recruitment of nectin into chimera junctions is mediated by the actin-binding domain of α-catenin. Our data suggests that E-cadherin regulates assembly of nectin junctions through α-catenin-induced remodeling of the actin cytoskeleton around the cadherin clusters.
Department of Dermatology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA.
Regina B
RB
Troyanovsky
Department of Dermatology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA.
Indrajyoti
I
Indra
Department of Dermatology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA.
Chi-Shuo
CS
Chen
Department of Dermatology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA.
Soonjin
S
Hong
Department of Dermatology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA s-troyanovsky@northwestern.edu.
Sergey M
SM
Troyanovsky
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D000075983:Nectins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; D015815:Cell Adhesion Molecules; D000075983:Nectins; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin
Actin; Adhesion; Cadherin; Nectin; α-catenin