Ion Channel Clustering at the Axon Initial Segment and Node of Ranvier Evolved Sequentially in Early Chordates
Figure 3
The NaV channel DII–III intracellular loop is poorly conserved in invertebrates lacking the anchor motif, and highly conserved in vertebrates.
(A) Plot showing lengths of DII–III loop sequences of NaV channels, deduced from cDNA clones. Stick bars show range, grey boxes show 2nd and 3rd quartiles, and red diamond shows average length. Black diamonds show lengths of loops from species indicated. (B–D) Cartoons depicting the degree of sequence conservation and exon borders (red bars) of orthologous NaV channels from D. melanogaster (para), C. intestinalis (Nav1), and H. sapiens (Nav1.1) in the region between D II S6 and DIII S1. Each shaded circle is one amino acid. In non-chordates (e.g., fly), the transmembrane and very membrane-proximal portions of the intracellular loop show high conservation with vertebrates, but the remainder of the loops are poorly conserved in sequence and length. In protochordates (e.g., C. intestinalis), a series of highly conserved residues (VPIAAIESDLDN, residues labeled) appears on a short, novel exon (red line in C); the rest of the loop is poorly conserved like other invertebrate genes. However, the mean length of the 4 known protochordate NaV1 loops is nearly identical to those of vertebrates. Among vertebrate genes (e.g., human Nav1.1), the entire loop is more highly conserved, and has a simplified exon structure, with the anchor motif part of the same, exceptionally long exon as the conserved DII6 transmembrane segment. The shading scheme is based on alignment of the indicated sequence and six vertebrate NaV channel sequences. Shading scale represents, from darkest to lightest, matching of 5–6 of 6, 3–4 of 6, 2 of 6, and 0–1 of 6 vertebrate sequences.