ATP depletion of tubular cells causes dissociation of the zonula adherens and nuclear translocation of beta-catenin and LEF-1.
This study examined the events associated with the reversible disruption of the structural and functional integrity of the zonula occludens (ZA) induced by ATP depletion of renal tubular cells. It shows that loss of the ZA after ATP depletion is associated with the withdrawal of E-cadherin, alpha-catenin, and beta-catenin, probably as intact cadherin-catenin complexes from the basolateral membrane of tubular cells. The relative amounts of all three proteins increased in the Triton X-100-insoluble fraction of cell lysates and decreased in the Triton X-100-soluble pool. These changes were reversed with repletion of cell ATP. It is additionally shown that ATP depletion induces nuclear translocation of beta-catenin and T cell factor (TCF)/lymphoid enhancer factor-1 (LEF-1), a transcriptional factor with which beta-catenin associates. The redistribution of the ZA proteins as intact E-cadherin-catenin complexes from the plasma membrane facilitates the rapid recovery of the ZA after sublethal ischemic injury. The translocation of beta-catenin and TCF/LEF-1 to the nucleus indicates that ATP depletion may activate the wnt/wingless signal transduction pathway. Thus, entirely novel evidence is provided that both of the known roles of beta-catenin, as a structural part of the ZA and as a component of the wnt/wingless pathway, play a role after sublethal ischemic injury to tubular cells. It is also speculated that the nuclear translocation of beta-catenin and TCF/LEF-1 modulates gene expression after ischemic injury and may contribute to events necessary for renal regeneration and repair after ischemic injury.
Price
Valerie R
VR
Renal Section, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Reed
Christine A
CA
Lieberthal
Wilfred
W
Schwartz
John H
JH
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1; D009893:Opossums; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000255:Adenosine Triphosphate