Unique gene structure and paralogy define the 7D-cadherin family

Abstract

Abstract. Cadherins are Ca 2+ -dependent transmembrane glycoproteins crucial for cell-cell adhesion in vertebrates and invertebrates. Classification of this superfamily due to their phylogenetic relationship is currently restricted to three major subfamilies: classical, desmosomal and protocadherins. Here we report evidence for a common phylogenetic origin of the kidney-specific Ksp-(Cdh16) and the intestine-specific LI-cadherin (Cdh17). Both genes consist of 18 exons and the positions of their exon-intron boundaries as well as their intron phases are perfectly conserved. We found an extensive paralogy of more than 40 megabases in mammals as well as teleost fish species encompassing the Ksp-and LI-cadherin genes. A comparable paralogy was not detected for other cadherin gene loci. These findings suggest that the Ksp-and LI-cadherin genes originated by chromosomal duplication early during vertebrate evolution and support our assumption that both proteins are paralogues within a separate cadherin family that we have termed 7D-cadherins.

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

“…LI-cadherin (cadherin-17) is evenly distributed along the lateral contact zones of enterocytes but is excluded from adherens junctions, 15 which are formed by E-cadherin and the cytoplasmic proteins β-catenin, p120-catenin, and α-catenin. 14,17 LI-cadherin belongs to a distinct group within the cadherin superfamily denoted as 7D-cadherins (seven-domain cadherins 18,19 ). In contrast to classical cadherins, LI-cadherin is composed of seven extracellular cadherin repeats and a cytoplasmic domain of only 25 amino acids that shares no similarity to the highly conserved cytoplasmic region of classical cadherins necessary for the interaction with β-and p120-catenin.…”

Intestinal LI-cadherin Acts as a Ca2+-dependent Adhesion Switch

“…13,14 E-cadherin is the prototype of classical cadherins which are composed of an extracellular part with five cadherin repeats, a single transmembrane domain and a highly conserved cytoplasmic region that links them to the actin cytoskeleton. 15,16 In contrast, LIcadherin belongs to the 7D-cadherin subfamily [17][18][19] and consists of seven extracellular cadherin repeats, a single transmembrane region and a cytoplasmic domain comprising only about 25 amino acid residues. 20 Both, E-cadherin and LI-cadherin are expressed in the enterocytes along the entire cryptvillus axis of the intestinal epithelium but exhibit a different subcellular localization.…”

“…For the renal interstitial fluid Ca 2+ concentrations of 1.63(±0.19) mM (cortex) and 1.93(±0.12) mM (medulla) were determined. 52,53 Interestingly, the kidney-specific Ksp-cadherin, the only other known 7D-cadherin, 19 shows a restricted expression pattern in the epithelium of the distal tubuli and of the collecting duct. 18,54 Both, the intestinal and the renal epithelia are sites of large volume water resorption and therefore might require an adhesive mechanism for the lateral cell surface that is sensitive to low extracellular Ca 2+ in order to allow extensive volume transport by increasing the lateral intercellular space.…”

Sorting out a promiscuous superfamily: towards cadherin connectomics

“…For instance, CDH13 (T-cadherin) with five EC repeats, is unique as it lacks transmembrane and cytoplasmic domains and is anchored to the membrane through a glycophosphatidylinositol (GPI) moiety [45,46]. The non-classical cadherins CDH16 and CDH17 have seven EC repeats and very short cytoplasmic domains [47–49]. On the protocadherin side, three gene clusters (α, β, and γ) code for a large number of proteins (a total of ~60 in most mammalian species) each with six EC repeats and a single pass transmembrane domain.…”