Biochemical characterization and functional analysis of two type II classic cadherins, cadherin-6 and -14, and comparison with E-cadherin.
Classic cadherins can be grouped based on their deduced primary structures. Among them the type I cadherins have been well characterized; however, little is known about non-type I cadherins. In this study we characterized two human type II cadherins, cadherin-6 and cadherin-14, using a cDNA transfection system. They were each detected as two bands electrophoretically, were expressed on the external cell surface at cell-cell contact sites, and were associated with caten- ins. Direct sequencing of the N-terminal amino acids showed that the two bands of cadherin-14 corresponded to precursor and mature forms, whereas the two bands of cadherin-6 both had the N-terminal sequence of the mature form. Unlike type I cadherins, both cadherin-6 and -14 were not protected from trypsin degradation by Ca2+. We evaluated their adhesive functions by a long term cell aggregation method. The results suggest that both cadherin-6 and -14 have cell-cell binding strengths virtually equivalent to that of E-cadherin and that their binding specificities are distinct from that of E-cadherin. Cadherin-6 and -14 interacted with each other in an incomplete manner. They have a QAI tripeptide in the first extracellular subdomain instead of the HAV motif that is characteristic of type I cadherins and is intimately involved in the adhesive function. The QAI tripeptide, however, appeared not to be involved in the adhesive functions of cadherin-6 and -14.
Shimoyama
Y
Y
Hirohashi Cell Configuration Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, Tsukuba Research Consortium, 5-9-4 Tokodai, Tsukuba 300-2635, Japan.
Takeda
H
H
Yoshihara
S
S
Kitajima
M
M
Hirohashi
S
S
D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002449:Cell Aggregation; D002478:Cells, Cultured; D018076:DNA, Complementary; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice
C104822:CDH18 protein, human; D015820:Cadherins; D018076:DNA, Complementary; C087310:K cadherin