ABSTRACT
delta-Protocadherins constitute a group of cadherins characterized by several conserved motifs in their cytoplasmic domains. We present a phylogenetic analysis that further divides this group into delta1-protocadherins (comprising protocadherin-1, -7, -9 and -11 or -X/Y) and delta2-protocadherins (comprising protocadherin-8, -10, -17, -18 and -19). The delta-protocadherin genes, which are located on different chromosomes in man and mouse, have a similar gene structure. They are expressed as multiple splice forms, differing mostly in their cytoplasmic domains. Some delta-protocadherins were reported to mediate weak cell-cell adhesion in vitro and cell sorting in vivo. In addition, individual delta-protocadherins might play important roles in signaling pathways, as they bind to proteins such as TAF1/Set, protein phosphatase-1alpha and the Frizzled 7 receptor. The spatiotemporally restricted expression of delta-protocadherins in different tissues and species and the results of their functional analysis, mainly in Xenopus, suggest that they play multiple, tightly regulated roles in vertebrate development.
Subject(s)
Cadherins/genetics , Cadherins/physiology , Alternative Splicing , Amino Acid Motifs , Animals , Cell Adhesion/physiology , Humans , Phylogeny , Signal Transduction/physiologyABSTRACT
Phylogenetic analysis of protocadherin genes identified a new gene subfamily, the delta-protocadherins, containing several conserved motifs in their cytoplasmic domains. This subfamily can be further subdivided into two subgroups, named delta1-protocadherins (comprising protocadherin-1, -7, -9, and -11 or X/Y) and delta2-protocadherins (comprising protocadherin-8, -10, -17, -18, and -19). The members of the delta1-protocadherin subgroup were analyzed in greater detail here. They share a similar gene structure that results in the expression of multiple alternative transcripts. All members of this subgroup have at least one transcript that contains a binding site for protein phosphatase-1alpha. Like most classic cadherins, each of three delta1-protocadherins analyzed in this study by in situ hybridization showed a unique expression pattern that differed from the patterns of the other delta1-protocadherins. Together, these results suggest that the members of the delta1-protocadherin subgroup exercise tightly regulated functions in the development, regionalization, and functional differentiation of the mouse brain.
Subject(s)
Brain/metabolism , Cadherins/genetics , Multigene Family/genetics , Amino Acid Sequence , Animals , Cadherins/metabolism , Cloning, Molecular , Gene Expression , Gene Library , Humans , In Situ Hybridization , Mice , Molecular Sequence Data , Phylogeny , Sequence AlignmentABSTRACT
Extensive cDNA analysis demonstrated that all human and mouse protocadherin-beta genes are one-exon genes. The protein sequences of these genes are highly conserved, especially the three most membrane-proximal extracellular domains. Phylogenetic analysis suggested that this unique gene family evolved by duplication of one single protocadherin-beta gene to 15 copies. The final difference in the number of protocadherin-beta genes in man (#19) and mouse (#22) is probably caused by duplications later in evolution. The complex relationship between human and mouse genes and the lack of pseudogenes in the mouse protocadherin-beta gene cluster suggest a species-specific evolutionary pressure for maintenance of numerous protocadherin-beta genes.
Subject(s)
Cadherins/genetics , Conserved Sequence/genetics , Evolution, Molecular , Multigene Family/genetics , Protein Precursors/genetics , Amino Acid Sequence , Animals , Exons , Gene Dosage , Gene Duplication , Humans , Mice , Molecular Sequence Data , Phylogeny , Sequence AlignmentABSTRACT
In a quest for novel cadherin gene family members in the human dbEST database, an interesting EST clone was identified and chosen for subsequent analysis. Using the technique of 5' rapid amplification of cDNA ends, we isolated the complete coding sequence and a large part of the UTRs of a novel gene. The sequence appeared to correspond to the human cadherin-10 gene, whose sequence was only partially known before. The expression pattern of this cadherin was found to be largely brain-specific, with additional expression in both adult and fetal kidney, and with minor expression in prostate and fetal lung. By FISH analysis the genomic location was determined at human chromosome 5p13-14, which is nearby the reported positions of the human cadherin-6, -12, and cadherin-14 (CDH18) genes. Cadherin-10 shows high relationship to the human cadherin-6 gene.