Heterotypic trans-interaction of LI- and E-cadherin and their localization in plasmalemmal microdomains.
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.
Baumgartner
Werner
W
Department of Cellular Neurobionics, Institute of Zoology, RWTH-Aachen University, D-52056 Aachen, Germany. werner@bio2.rwth-aachen.de
Wendeler
Markus W
MW
Weth
Agnes
A
Koob
Rainer
R
Drenckhahn
Detlev
D
Gessner
Reinhard
R
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018625:Microscopy, Atomic Force
C490584:CDH17 protein, human; D015820:Cadherins