Yessotoxin induces the accumulation of altered E-cadherin dimers that are not part of adhesive structures in intact cells.
We have studied the alteration induced by yessotoxin in the E-cadherin-catenin system of epithelial cells by stabilizing the protein-protein interactions in oligomers, through the introduction of covalent bonds between subunits in vitro and in vivo. The E-cadherin-catenin complexes that we have stabilized by crosslinking comprise multiple forms of dimeric, trimeric, tetrameric and hexameric complexes, with different subunit compositions. A 1-day treatment of MCF-7 cells with yessotoxin resulted in an increase in cellular levels of the complexes including a 100kDa fragment of E-cadherin (ECRA100), with a relative increase in cellular E-cadherin .ECRA100 heterodimers, as opposed to the E-cadherin homodimer that represents the core structure of the E-cadherin-catenin system of adhesive structures in normal cells. The high MW oligomers of cell adhesive structures, in turn, were not appreciably altered by cell treatment with yessotoxin. Most of these oligomers partitioned in a fraction that cannot be solubilized by non-ionic detergents after crosslinking of intact cells. Yessotoxin treatment did not significantly alter the levels of ECRA100 in the Triton X-100 resistant fraction of plasma membrane, but increased the relative abundance of ECRA100 in the Triton X-100 soluble pool of crosslinked cells. We have concluded that cell exposure to yessotoxin leads to increased cellular contents of E-cadherin .ECRA100 heterodimers that are not participating to cell adhesive structures but are located in other membranous fractions of intact cells.
D015820:Cadherins / Q000378:metabolism* / Q000502:physiology; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003902:Detergents; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005976:Glutaral / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D008978:Mollusk Venoms / Q000494:pharmacology*; D017830:Octoxynol; D035964:Oxocins / Q000494:pharmacology*
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; D003902:Detergents; D004988:Ethers, Cyclic; D008978:Mollusk Venoms; D035964:Oxocins; D017830:Octoxynol; C066632:yessotoxin; D005976:Glutaral