Figure 6
Phenylalanine substitution of the cognate valine in C. elegans kcnl-2 ameliorates SOD1G85R ALS model locomotion defects. (a) Amino acid sequence alignment of mammalian SK2 channels and orthologous C. elegans KCNL-2 at the region connecting the CaMBD and the S6 transmembrane domain. Amino acids are numbered according to KCNL-2 isoform j. Seven amino acid residues from the IDF shown in magenta are the focus of this study. Human and rat SK2 sequences are identical in this region. (b) Diagram: to measure locomotion defects, adult animals were scored for dispersal 1 hour after they were placed at the center of a thin bacterial lawn on a 60-mm petri dish (food source). Coordinated animals disperse radially from the center of the bacterial lawn. Uncoordinated animals disperse more slowly. (c) Pan-neuronal expression of hSOD1G85R slowed dispersal, compared to hSOD1WT controls (one-tailed t-test, P = 0.0006; n = 60). Phenylalanine substitution of the cognate valine in C. elegans kcnl-2 increased dispersal in hSOD1G85R animals, compared to hSOD1G85R animals carrying the kcnl-2 wild type allele (one-tailed t-test, P = 0.0105; n = 60). Each determination is average of four trials. All data are presented in mean ± s.e.m. All animals were tested in sod-1(tm776) null background.
