Heterotypic trans-Interaction of LI- and E-Cadherin and Their Localization in Plasmalemmal Microdomains

• Published in: Journal of molecular biology 2008-04, Vol.378 (1), p.44-54
• Main Authors: Baumgartner, Werner, Wendeler, Markus W., Weth, Agnes, Koob, Rainer, Drenckhahn, Detlev, Geßner, Reinhard
• Format: Article
• Language: English
• Subjects: 7D-cadherin; adhesion; AFM; Animals; Cadherins - analysis; Cadherins - metabolism; CHO Cells; cholesterol; Cricetinae; Cricetulus; enterocyte; Humans; Membrane Microdomains - chemistry; Membrane Microdomains - metabolism; Mice; Microscopy, Atomic Force
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2008.02.023

Cadherins are calcium-dependent adhesion molecules important for tissue morphogenesis and integrity. LI-cadherin and E-cadherin are the two prominent cadherins in intestinal epithelial cells. Whereas LI-cadherin belongs to the subfamily of 7D (seven-domain)-cadherins defined by their seven extracellular cadherin repeats and short intracellular domain, E-cadherin is the prototype of classical cadherins with five extracellular domains and a highly conserved cytoplasmic part that interacts with catenins and thereby modulates the organization of the cytoskeleton. Here, we report a specific heterotypic trans-interaction of LI- with E-cadherin, two cadherins of distinct subfamilies. Using atomic force microscopy and laser tweezer experiments, the trans-interaction of LI- and E-cadherin was characterized on the single-molecule level and on the cellular level, respectively. This heterotypic interaction showed similar binding strength (20–52 pN at 200–4000 nm/s) and lifetime (0.8 s) as the respective homotypic interactions of LI- and E-cadherin. VE-cadherin, another classical cadherin, did not bind to LI-cadherin. In enterocytes, LI-cadherin and E-cadherin are located in different membrane regions. LI-cadherin is distributed along the basolateral membrane, whereas the majority of E-cadherin is concentrated in adherens junctions. This difference in membrane distribution was also reflected in Chinese hamster ovary cells stably expressing either LI- or E-cadherin. We found that LI-cadherin is localized almost exclusively in cholesterol-rich fractions, whereas E-cadherin is excluded from these membrane fractions. Given their different membrane localization in enterocytes, the heterotypic trans-interaction of LI- and E-cadherin might play a role during development of the intestinal epithelium when the cells do not yet have elaborate membrane specializations.