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To understand the mechanism of this effect we have examined how removal of calcium ions from the culture medium of A-431 epithelial cells affects complexes incorporating the cell-cell adhesive receptors, E-cadherin, desmoglein or desmocollin. Sedimentation and biochemical analysis demonstrated that calcium removal triggers a rapid formation of a novel type of complex formed via direct lateral E-cadherin-desmoglein, E-cadherin-desmocollin and desmoglein-desmocollin dimerization of the extracellular cadherin regions. Replacement of Trp156 and Val157 of E-cadherin, that has been shown to abolish lateral and adhesive E-cadherin homodimerization in standard cultures, did not influence the formation of these calcium-sensitive complexes. Furthermore, experiments with this mutant revealed that EGTA induced lateral Trp156\/Val157-independent homodimerization of E-cadherin. Deletion mutagenesis of E-cadherin showed that these complexes are mediated by at least two extracellular cadherin domains, EC3 and EC4. Notably, protein kinase inhibitor H-7 which confers EGTA-independence of the adhesive E-cadherin complexes does not block this association. We propose that this novel type of intercadherin interaction is involved in the assembly of adherens junctions and their disassembly in low-calcium medium.<\/jats:p>","DOI":"10.1242\/jcs.112.23.4379","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T17:30:06Z","timestamp":1619371806000},"page":"4379-4387","source":"Crossref","is-referenced-by-count":34,"title":["Removal of calcium ions triggers a novel type of intercadherin interaction"],"prefix":"10.1242","volume":"112","author":[{"given":"Regina B.","family":"Troyanovsky","sequence":"first","affiliation":[{"name":"Washington University Medical School, St Louis Division of Dermatology , , MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Klingelh\u00f6fer","sequence":"additional","affiliation":[{"name":"Washington University Medical School, St Louis Division of Dermatology , , MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Troyanovsky","sequence":"additional","affiliation":[{"name":"Washington University Medical School, St Louis Division of Dermatology , , MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,12,1]]},"reference":[{"key":"2024071016370742500_JOCES_112_23_4379C1","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1083\/jcb.135.6.1899","article-title":"Quantitative analysis of cadherin-catenin-actin reorganization during development of cell-cell adhesion","volume":"135","author":"Adams","year":"1996","journal-title":"J. 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