Separation force measurements reveal different types of modulation of E-cadherin-based adhesion by nectin-1 and -3.
Nectins are Ca2+-independent cell adhesion molecules found at cadherin-based adherens junctions. We used a dual pipette assay that measures the forces required to separate cell doublets to determine how nectins affect the formation and strength of cell-cell adhesion. Less force was required to separate doublets of L cells expressing nectin-1 or nectin-3 than to separate doublets of E-cadherin-expressing cells. Heterodimers formed between cells expressing nectin-1 or nectin-3 adhered more strongly than homodimers. Nectin-3 that does not trans-interact with nectin-1 inhibited E-cadherin-mediated adhesion. However, the extracellular fragment of nectin-1 did not have an agonistic effect on E-cadherin-dependent cell adhesion when it trans-interacted with nectin-3, expressed at high levels in cells. In contrast, the extracellular fragment of nectin-3 had a significant agonistic effect on cadherin-based adhesion when it interacted with endogenous nectin-1, expressed at low levels in cells. Our results indicate that E-cadherin is the key molecule involved in cell adhesion and that the regulation of E-cadherin-based adhesion involving cellular nectin-1 trans-interacting with nectin-3 is qualitatively different from that involving cellular nectin-3 trans-interacting with nectin-1 and depends on the nectin levels expressed by cells.
Martinez-Rico
Clara
C
UMR 144 CNRS-Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Pincet
Frederic
F
Perez
Eric
E
Thiery
Jean Paul
JP
Shimizu
Kazuya
K
Takai
Yoshimi
Y
Dufour
Sylvie
S
D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D000075983:Nectins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D013997:Time Factors
D015820:Cadherins; D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619014:NECTIN3 protein, human; C000619015:Nectin1 protein, mouse; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D002118:Calcium