LI-cadherin cis-dimerizes in the plasma membrane Ca2+ independently and forms highly dynamic trans-contacts

• Published in: Cellular and molecular life sciences : CMLS 2012-11, Vol.69 (22), p.3851-3862
• Main Authors: Bartolmäs, Thilo, Hirschfeld-Ihlow, Caroline, Jonas, Sven, Schaefer, Michael, Geßner, Reinhard
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Life Sciences; Research Article
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-012-1053-y

LI-cadherin belongs to the family of 7D-cadherins that is characterized by a low sequence similarity to classical cadherins, seven extracellular cadherin repeats (ECs), and a short cytoplasmic domain. Nevertheless, LI-cadherins mediates Ca 2+ -dependent cell–cell adhesion and induces an epitheloid cellular phenotype in non-polarized CHO cells. Whereas several studies suggest that classical cadherins cis -dimerize in a Ca 2+ -dependent manner and interact in trans by strand-swapping tryptophan 2 of EC1, little is known about the molecular interactions of LI-cadherin, which lacks tryptophan 2. We thus expressed fluorescent LI-cadherin fusion proteins in HEK293 and CHO cells, analyzed their cell–cell adhesive properties and studied their cellular distribution, cis -interaction, and lateral diffusion in the presence and absence of Ca 2+ . LI-cadherin highly concentrates in cell contact areas but rapidly leaves those sites upon Ca 2+ depletion and redistributes evenly on the cell surface, indicating that it is only kept in the contact areas by trans -interactions. Fluorescence resonance energy transfer analysis of LI-cadherin-CFP and -YFP revealed that LI-cadherin forms cis -dimers that resist Ca 2+ depletion. As determined by fluorescence redistribution after photobleaching, LI-cadherin freely diffuses in the plasma membrane as a cis -dimer ( D  = 0.42 ± 0.03 μm 2 /s). When trapped by trans -binding in cell contact areas, its diffusion coefficient decreases only threefold to D  = 0.12 ± 0.01 μm 2 /s, revealing that, in contrast to classical and desmosomal cadherins, trans -contacts formed by LI-cadherin are highly dynamic.