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. 2006 Mar 8;26(10):2599–2613. doi: 10.1523/JNEUROSCI.4314-05.2006

Figure 8.

Figure 8.

The ankyrin-G binding motifs of NaV channel α subunits and KCNQ2/KCNQ3 subunits appear first in lower vertebrates, apparently reflecting a process of convergent molecular evolution. A, Clustal alignment was performed on full-length predicted amino acid sequences of invertebrates and vertebrate NaV α subunits. The positions corresponding to the ankyrin-G binding motifs and the conserved DIII–DIV intracellular linker mediating fast inactivation are shown. Ankyrin-G binding motifs are absent from invertebrates, but are present in teleost fish and mammals. B, Alignments made, as in A, but of KCNQ channel subunits of invertebrates and vertebrates. A portion of the highly conserved KCNQ C2 domain, mediating subunit association, and the ankyrin-G binding motif are shown. The ankyrin-G binding motif is absent from invertebrate genes but is present in KCNQ2 and KCNQ3 of teleost fish, birds, and mammals. For genes with accession numbers AAN63887, CAA11526, CAF90163, and AAV34442, we assigned KCNQ family identity based on high homology with known KCNQ genes identified by BLASTp analysis. For A and B, species name and NCBI protein database accession numbers are indicated in parentheses. C, Phylogenetic tree of Aplysia NaV and representative KCNQ channels. The analysis confirms the very distant evolutionary relationship between NaV and KCNQ channels and illustrates the close paralogous relationship between KCNQ2 and KCNQ3. This suggests that the appearance of the similar ankyrin-G binding motifs in NaV and KCNQ2/KCNQ3 genes took place independently, before the last common ancestor of jawed vertebrates. Scale bar, absolute number of changed residues. D, Diagram showing proposed interactions between NaV channels, KCNQ channels, ankyrin-G, and the actin–βIV spectrin cortical cytoskeleton at AISs and nodes. For simplicity, other known membrane proteins of nodes and AISs (neurofascin and relate cell adhesion molecules; NaV channel β subunits) are not depicted. The stoichiometry of interactions between ankyrin-G and membrane proteins is unknown.