p120-catenin is a key component of the cadherin-gamma-secretase supercomplex.
In this work, we show several previously unknown features of p120-catenin in a cadherin-catenin complex that are critical for our understanding of cadherin-based adhesion and signaling. We show that in human epithelial A-431 cells, nearly all p120 molecules engage in high-affinity interaction with E-cadherin-catenin complexes located at the cellular surface. p120 is positioned in proximity to alpha-catenin in the complex with cadherin. These findings suggest a functional cooperation between p120 and alpha-catenin in cadherin-based adhesion. A low level of cadherin-free p120 molecules, in contrast, could facilitate p120-dependent signaling. Finally, we present compelling evidence that p120 is a key linker cementing the E-cadherin-catenin complex with the transmembrane protease gamma-secretase. The cell-cell contact location of this supercomplex makes it an important candidate for conducting different signals that rely on gamma-secretase proteolytic activity.
Kiss
Alexi
A
Division of Dermatology, Washington University Medical School, St. Louis, MO 63110, USA.
Troyanovsky
Regina B
RB
Troyanovsky
Sergey M
SM
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D053829:Amyloid Precursor Protein Secretases; D000095002:Delta Catenin; C000722347:CTNND1 protein, human