Key result
Deletion of the ankyrin-G-binding motif in KCNQ3, but not KCNQ2 alone, significantly reduces the enrichment of the KCNQ2/3 channel complex at the axon initial segment.
KCNQ3 is a major determinant of M channel localization to the axon initial segment via its ankyrin-G-binding motif.
Preclinical only; leaves open whether KCNQ3 motif targeting could modulate excitability in channelopathies.
The potassium channel subunits KCNQ2 and KCNQ3 are believed to underlie the M current of hippocampal neurons. The M-type potassium current plays a key role in the regulation of neuronal excitability; however, the subcellular location of the ion channels underlying this regulation has been controversial. We report here that KCNQ2 and KCNQ3 subunits are localized to the axon initial segment of pyramidal neurons of adult rat hippocampus and in cultured hippocampal neurons. We demonstrate that the localization of the KCNQ2/3 channel complex to the axon initial segment is favored by co-expression of the two channel subunits. Deletion of the ankyrin-G-binding motif in both the KCNQ2 and KCNQ3 C-terminals leads to the disappearance of the complex from the axon initial segment, albeit the channel complex remains functional and still reaches the plasma membrane. We further show that although heteromeric assembly of the channel complex favours localization to the axon initial segment, deletion of the ankyrin-G-binding motif in KCNQ2 alone does not alter the subcellular localization of KCNQ2/3 heteromers. By contrast, deletion of the ankyrin-G-binding motif in KCNQ3 significantly reduces AIS enrichment of the complex, implicating KCNQ3 as a major determinant of M channel localization to the AIS.
No takes yet. Share an insight, caveat, or question.
Rasmussen et al. (2007) studied this question. Deletion of the ankyrin-G-binding motif in KCNQ2 and KCNQ3 vs. Wild-type KCNQ2/3 co-expression was evaluated on Localization of the KCNQ2/3 channel complex to the axon initial segment. Deletion of the ankyrin-G-binding motif in KCNQ3, but not KCNQ2 alone, significantly reduces the enrichment of the KCNQ2/3 channel complex at the axon initial segment.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: