Intestinal LI-cadherin acts as a Ca2+-dependent adhesion switch.
Cadherins are Ca(2+)-dependent transmembrane glycoproteins that mediate cell-cell adhesion and are important for the structural integrity of epithelia. LI-cadherin and the classical E-cadherin are the predominant two cadherins in the intestinal epithelium. LI-cadherin consists of seven extracellular cadherin repeats and a short cytoplasmic part that does not interact with catenins. In contrast, E-cadherin is composed of five cadherin repeats and a large cytoplasmic domain that is linked via catenins to the actin cytoskeleton. Whereas E-cadherin is concentrated in adherens junctions, LI-cadherin is evenly distributed along the lateral contact area of intestinal epithelial cells. To investigate if the particular structural properties of LI-cadherin result in a divergent homotypic adhesion mechanism, we analyzed the binding parameters of LI-cadherin on the single molecule and the cellular level using atomic force microscopy, affinity chromatography and laser tweezer experiments. Homotypic trans-interaction of LI-cadherin exhibits low affinity binding with a short lifetime of only 1.4 s. Interestingly, LI-cadherin binding responds to small changes in extracellular Ca(2+) below the physiological plasma concentration with a high degree of cooperativity. Thus, LI-cadherin might serve as a Ca(2+)-regulated switch for the adhesive system on basolateral membranes of the intestinal epithelium.
Wendeler
Markus W
MW
Biomedical Research Center, Virchow Hospital of Charité Medical School Berlin, D-13353 Berlin, Germany.
Drenckhahn
Detlev
D
Gessner
Reinhard
R
Baumgartner
Werner
W
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002846:Chromatography, Affinity; D006224:Cricetinae; D003412:Cricetulus; D007422:Intestines / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D018625:Microscopy, Atomic Force; D052898:Optical Tweezers; D017434:Protein Structure, Tertiary
D015820:Cadherins; C490585:Cdh17 protein, mouse; D002118:Calcium