Ankyrin-G binding motif of KCNQ2-3
|Ankyrin-G binding motif of KCNQ2-3|
Interactions with ankyrin-G (ankyrin-3) are crucial to the localisation of voltage-gated sodium channels (VGSCs) at the axon initial segment and for neurons to initiate action potentials. This conserved 9-amino acid motif ((V/A)P(I/L)AXXE(S/D)D) is required for ankyrin-G binding and functions to localise sodium channels to a variety of 'excitable' membrane domains both inside and outside of the nervous system. This motif has also been identified in the potassium channel 6TM proteins KCNQ2 and KCNQ3  that correspond to the M channels that exert a crucial influence over neuronal excitability. KCNQ2/KCNQ3 channels are preferentially localised to the surface of axons both at the axonal initial segment and more distally, and this axonal initial segment targeting of surface KCNQ channels is mediated by these ankyrin-G binding motifs of KCNQ2 and KCNQ3. KCNQ3 is a major determinant of M channel localisation to the AIS, rather than KCNQ2. Phylogenetic analysis reveals that anchor motifs evolved sequentially in chordates (NaV channel) and jawed vertebrates (KCNQ2/3).
- Lemaillet G, Walker B, Lambert S (July 2003). "Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits". J. Biol. Chem. 278 (30): 27333–9. doi:10.1074/jbc.M303327200. PMID 12716895.
- Pan Z, Kao T, Horvath Z, Lemos J, Sul JY, Cranstoun SD, Bennett V, Scherer SS, Cooper EC (March 2006). "A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon". J. Neurosci. 26 (10): 2599–613. doi:10.1523/JNEUROSCI.4314-05.2006. PMID 16525039.
- Chung HJ, Jan YN, Jan LY (June 2006). "Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains". Proc. Natl. Acad. Sci. U.S.A. 103 (23): 8870–5. doi:10.1073/pnas.0603376103. PMC 1472242. PMID 16735477.
- Rasmussen HB, Frøkjaer-Jensen C, Jensen CS, Jensen HS, Jørgensen NK, Misonou H, Trimmer JS, Olesen SP, Schmitt N (March 2007). "Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment". J. Cell Sci. 120 (Pt 6): 953–63. doi:10.1242/jcs.03396. PMID 17311847.
- Hill AS, Nishino A, Nakajo K, Zhang G, Fineman JR, Selzer ME, Okamura Y, Cooper EC (December 2008). "Ion channel clustering at the axon initial segment and node of Ranvier evolved sequentially in early chordates". PLoS Genet. 4 (12): e1000317. doi:10.1371/journal.pgen.1000317. PMC 2597720. PMID 19112491.