LI-cadherin-mediated cell-cell adhesion does not require cytoplasmic interactions.
The adhesive function of classical cadherins depends on the association with cytoplasmic proteins, termed catenins, which serve as a link between cadherins and the actin cytoskeleton. LI-cadherin, a structurally different member of the cadherin family, mediates Ca2+-dependent cell-cell adhesion, although its markedly short cytoplasmic domain exhibits no homology to this highly conserved region of classical cadherins. We now examined whether the adhesive function of LI-cadherin depends on the interaction with catenins, the actin cytoskeleton or other cytoplasmic components. In contrast to classical cadherins, LI-cadherin, when expressed in mouse L cells, was neither associated with catenins nor did it induce an upregulation of beta-catenin. Consistent with these findings, LI-cadherin was not resistant to detergent extraction and did not induce a reorganization of the actin cytoskeleton. However, LI-cadherin was still able to mediate Ca2+-dependent cell-cell adhesion. To analyze whether this function requires any interaction with proteins other than catenins, a glycosyl phosphatidylinositol-anchored form of LI-cadherin (LI-cadherin(GPI)) was constructed and expressed in Drosophila S2 cells. The mutant protein was able to induce Ca2+-dependent, homophilic cell-cell adhesion, and its adhesive properties were indistinguishable from those of wild type LI-cadherin. These findings indicate that the adhesive function of LI-cadherin is independent of any interaction with cytoplasmic components, and consequently should not be sensitive to regulatory mechanisms affecting the binding of classical cadherins to catenins and to the cytoskeleton. Thus, we postulate that the adhesive function of LI-cadherin is complementary to that of coexpressed classical cadherins ensuring cell-cell contacts even under conditions that downregulate the function of classical cadherins.
Kreft
B
B
Institute of Clinical Chemistry and Biochemistry, Humboldt-University Berlin, Germany.
Berndorff
D
D
Böttinger
A
A
Finnemann
S
S
Wedlich
D
D
Hortsch
M
M
Tauber
R
R
Gessner
R
R
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila; D015870:Gene Expression; D017261:Glycosylphosphatidylinositols; D007739:L Cells; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D051381:Rats; D015534:Trans-Activators; D014162:Transfection; D051176:beta Catenin
D000199:Actins; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D002352:Carrier Proteins; C490585:Cdh17 protein, mouse; C490586:Cdh17 protein, rat; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D017261:Glycosylphosphatidylinositols; D026901:Membrane Transport Proteins; D015534:Trans-Activators; D051176:beta Catenin; C067802:intestinal peptide-proton cotransporter; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase