Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging

Abstract

The voltage-gated Na (+) channels (VGSC) are complex membrane proteins responsible for generation and propagation of the electrical signals through the brain, the skeletal muscle and the heart. The levels of sodium channels affect behavior and physical activity. This is illustrated by the maleless mutant allele (mle (napts)) in Drosophila, where the decreased levels of voltage-gated Na(+) channels cause temperature-sensitive paralysis. Here, we report that mle (napts) mutant flies exhibit developmental lethality, decreased fecundity and increased neurodegeneration. The negative effect of decreased levels of Na(+) channels on development and ts-paralysis was more pronounced at 18 and 29°C than at 25°C, suggesting particular sensitivity of the mle (napts) flies to temperatures above and below normal environmental conditions. Similarly, longevity of mle (napts) flies was unexpectedly short at 18 and 29°C compared with flies heterozygous for the mle (napts) mutation. Developmental lethality and neurodegeneration of mle (napts) flies was partially rescued by increasing the dosage of para, confirming a vital role of Na(+) channels in development, longevity and neurodegeneration of flies and their adaptation to temperatures.

Molecular characterization and functional expression of voltage‐gated sodium channel variants in Apolygus lucorum (Meyer‐Dür)

“…Two amino acid changes, I1640V and M1673I, resulted from A‐to‐I editing sites were previously reported in DmNa v transcripts and BgNa v transcripts, respecively Four other amino acid changes, R1339G, K1340E, R1653G and I1902M, are unique. Of these, R1339G is adjacent to K1340E, but they are not always edited at the same time, maybe because two adjacent RNA editing amino acids have similar post‐transcriptional modification function like double mutation, which cause sodium channel behavioral defects However, the effects of these amino acid changes and how the RNA editing takes on the role of sodium channel regulation of the nervous system still need to be verified. Identification of alternative splicing and RNA editing variants that have unique gating properties is a valuable resource to gain insights into specific amino acid sequences/residues that are critical for channel function and interactions of sodium channels with insecticides and other toxins.…”

Molecular biology of insect sodium channels and pyrethroid resistance

“…Even small changes in sodium channel expression and/or function could be biologically relevant, as underscored by sodium channel mutations that cause various behavioral defects in D. melanogaster (Garber et al, 2012; Lilly et al, 1994; Lindsay et al, 2008; Parker et al, 2011; Sun et al, 2012; Wang et al, 1997). In addition, identification of alternative splicing and RNA-editing variants that have unique gating properties provided a valuable resource to gain insights into specific amino acid sequences/residues that are critical for channel function and interactions of sodium channels with insecticides and other toxins (Du et al, 2006; Du et al, 2009c; Du et al, 2010; Silver et al, 2014; Song et al, 2011; Song et al, 2006; Tan et al, 2002a).…”

Tertiary structural elements determine the extent and specificity of messenger RNA editing

“…Sodium channel abundance affects Drosophila behaviour, development, reproduction and aging 39 . Flies hemi-or homozygous for the DCS zip allele are ts-paralytic (Fig.…”