α-Catenin-mediated cadherin clustering couples cadherin and actin dynamics.
The function of the actin-binding domain of α-catenin, αABD, including its possible role in the direct anchorage of the cadherin-catenin complex to the actin cytoskeleton, has remained uncertain. We identified two point mutations on the αABD surface that interfere with αABD binding to actin and used them to probe the role of α-catenin-actin interactions in adherens junctions. We found that the junctions directly bound to actin via αABD were more dynamic than the junctions bound to actin indirectly through vinculin and that recombinant αABD interacted with cortical actin but not with actin bundles. This interaction resulted in the formation of numerous short-lived cortex-bound αABD clusters. Our data suggest that αABD clustering drives the continuous assembly of transient, actin-associated cadherin-catenin clusters whose disassembly is maintained by actin depolymerization. It appears then that such actin-dependent αABD clustering is a unique molecular mechanism mediating both integrity and reassembly of the cell-cell adhesive interface formed through weak cis- and trans-intercadherin interactions.
Department of Dermatology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Chi-Shuo
CS
Chen
Department of Dermatology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Soonjin
S
Hong
Department of Dermatology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Indrajyoti
I
Indra
Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032 Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, NY 10032 Department of Systems Biology, Columbia University, New York, NY 10032.
Alina P
AP
Sergeeva
Department of Dermatology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Regina B
RB
Troyanovsky
Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032 Department of Systems Biology, Columbia University, New York, NY 10032 s-troyanovsky@northwestern.edu bh6@columbia.edu lss8@columbia.edu.
Lawrence
L
Shapiro
Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032 Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, NY 10032 Department of Systems Biology, Columbia University, New York, NY 10032 Howard Hughes Medical Institute, Chevy Chase, MD 20815 s-troyanovsky@northwestern.edu bh6@columbia.edu lss8@columbia.edu.
Barry
B
Honig
Department of Dermatology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 s-troyanovsky@northwestern.edu bh6@columbia.edu lss8@columbia.edu.
Sergey M
SM
Troyanovsky
D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007700:Kinetics; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D059008:Time-Lapse Imaging; D016596:Vinculin / Q000378:metabolism; D051178:alpha Catenin / Q000737:chemistry / Q000502:physiology*
D000199:Actins; C495273:CTNNA1 protein, human; D015820:Cadherins; C488955:VCL protein, human; D051178:alpha Catenin; D016596:Vinculin