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Tracing the evolution of nectin and nectin-like cell adhesion molecules - PubMed

  • ️Wed Jan 01 2020

Tracing the evolution of nectin and nectin-like cell adhesion molecules

Kheerthana Duraivelan et al. Sci Rep. 2020.

Abstract

Nectin and nectin-like cell adhesion molecules (collectively referred as nectin family henceforth) are known to mediate cell-cell adhesion and related functions. While current literature suggests that nectins are prevalent in vertebrates, there are no in-depth analyses regarding the evolution of nectin family as a whole. In this work, we examine the evolutionary origin of the nectin family, using selected multicellular metazoans representing diverse clades whose whole genome sequencing data is available. Our results show that this family may have appeared earlier during metazoan evolution than previously believed. Systematic analyses indicate the order in which various members of nectin family seem to have evolved, with some nectin-like molecules appearing first, followed by the evolution of other members. Furthermore, we also found a few possible ancient homologues of nectins. While our study confirms the previous grouping of the nectin family into nectins and nectin-like molecules, it also shows poliovirus receptor (PVR/nectin-like-5) to possess characteristics that are intermediate between these two groups. Interestingly, except for PVR, the other nectins show surprising sequence conservations across species, suggesting evolutionary constraints due to critical roles played by these proteins.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1

Phylogenetic tree of the 9 human nectin homologues. The evolutionary relationship between the 9 human nectin homologues was analysed with an unrooted phylogenetic tree created with PHYLIP package, using full-length sequences. The results indicate that the nectin family cluster into 2 distinct sub-groups, one consisting of 5 members: nectin-1 to -4 and PVR; the other with necl-1 to -4.

Figure 2
Figure 2

Multiple sequence alignments of the 2 sub-groups of the nectin family. Nectin-like molecules and nectins were aligned to look for consensus sequences. Nectin-like molecules (a) show higher sequence similarity compared to nectins (b). In nectins, the cytoplasmic region is not conserved, while in necls, even the cytoplasmic region shows high sequence similarities. Nectin-2 and PVR show high sequence identity (c), suggesting that they share a common ancestry.

Figure 3
Figure 3

Domain organization of nectin family members. Based on the multiple sequence alignments performed earlier, the domain organization of nectins are represented here. All 9 nectins have an extracellular region (EC) composed of 3 domains – an Ig V-like domain (EC1) followed by 2 Ig-C-like domains (EC2 and EC3), a transmembrane region (TM) and a cytoplasmic domain (CD), in addition to a signal sequence (SS) (a–d). However, there are some differences in the cytoplasmic motifs between nectins (a), PVR (b) and necls (c). Nectins (a) possess a PDZ-binding motif in their cytoplasm, while nectin-like molecules (c) contain a PDZ-binding motif as well as a band 4.1 binding motif. PVR, on the other hand contains only an ITIM motif (b).

Figure 4
Figure 4

Evolution of the nectin family in metazoans. Whole genome sequences of 39 organisms belonging to diverse clades of metazoans, were used in BLASTp search against the 9 human nectin homologues. After analyses, the evolutionary appearance of nectins were plotted into the phylogenetic tree of metazoans (not to scale). The clade-specific absences of nectins are shown in the figure represented as blank cells. Also, the numbers indicate the chromosomal location of each nectin gene, which suggests that the nectin family genes show chromosomal clustering during metazoan evolution.

Figure 5
Figure 5

Proteins with equidistant relationship to more than one human nectin. Coelacanth, a primitive fish contains nectin-1 and nectin-1-like, and lacks nectin-2. Since reverse blast to human proteome shows that nectin-1-like is equally related to both human nectin-1 and nectin-2, nectin-1-like may represent an intermediate between these two proteins.

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