Generation and characterization of new alleles of <i>quiver</i> (<i>qvr</i>) that encodes an extracellular modulator of the <i>Shaker</i> potassium channel

<p>Our earlier genetic screen uncovered a paraquat-sensitive leg-shaking mutant <i>quiver<sup>1</sup></i> (<i>qvr<sup>1</sup></i>), whose gene product interacts with the <i>Shaker</i> (<i>Sh</i>) K<sup>+</sup> channel. We also mapped the <i>qvr</i> locus to EY04063 and noticed altered day–night activity patterns in these mutants. Such circadian behavioral defects were independently reported by another group, who employed the <i>qvr<sup>1</sup></i> allele we supplied them, and attributed the extreme restless phenotype of EY04063 to the <i>qvr</i> gene. However, their report adopted a new noncanonical gene name <i>sleepless</i> (<i>sss</i>) for <i>qvr</i>. In addition to <i>qvr<sup>1</sup> </i>and <i>qvr<sup>EY</sup></i>, our continuous effort since the early 2000s generated a number of novel recessive <i>qvr</i> alleles, including ethyl methanesulfonate (EMS)-induced mutations <i>qvr<sup>2</sup></i> and <i>qvr<sup>3</sup></i>, and P-element excision lines <i>qvr<sup>ip6</sup></i> (imprecise jumpout), <i>qvr<sup>rv7</sup></i>, and <i>qvr<sup>rv9</sup></i> (revertants) derived from <i>qvr<sup>EY</sup></i>. Distinct from the original intron-located <i>qvr<sup>1</sup> </i>allele that generates abnormal-sized mRNAs, <i>qvr<sup>2</sup></i>, and <i>qvr<sup>3</sup></i> had their lesion sites in exons 6 and 7, respectively, producing nearly normal-sized mRNA products. A set of RNA-editing sites are nearby the lesion sites of <i>qvr<sup>3</sup></i> and <i>qvr<sup>EY</sup></i> on exon 7. Except for the revertants, all <i>qvr</i> alleles display a clear ether-induced leg-shaking phenotype just like <i>Sh</i>, and weakened climbing abilities to varying degrees. Unlike <i>Sh</i>, all shaking <i>qvr</i> alleles (except for <i>qvr<sup>f01257</sup></i>) displayed a unique activity-dependent enhancement in excitatory junction potentials (EJPs) at larval neuromuscular junctions (NMJs) at very low stimulus frequencies, with <i>qvr<sup>EY</sup></i> displaying the largest EJP and more significant NMJ overgrowth than other alleles. Our detailed characterization of a collection of <i>qvr</i> alleles helps to establish links between novel molecular lesions and different behavioral and physiological consequences, revealing how modifications of the <i>qvr</i> gene lead to a wide spectrum of phenotypes, including neuromuscular hyperexcitability, defective motor ability and activity-rest cycles.</p>