Worm Breeder's Gazette 13(5): 30 (February 1, 1995)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Department of Genetics, SK-50, University of Washington, Seattle, WA 98195
We have analyzed a large number of genes that we believe act in muscle activation (Mac). Here we describe mutations that are muscle activation-defective (Mac-d) and muscle hyper-activated (Mac-h). Mutations in the following genes are Mac-d: egl-2, egl-l9, egl-23, egl-30, egl-36, exp-2, exp-3, exp-4, unc-93, sup-9, sup-10, and unc-103. Our main criterion for this group is phenotypic similarity to muscle structure mutants (e.g. unc-54), with the exception that Mac mutants generally display more ability for muscle contractility. This point is best illustrated by an archetypal Mac-d mutation, unc-93(el500sd). el500sd mutant animals are "rubber-band" Uncs: they are flaccidly paralyzed and slightly long, similar to unc-54 mutants. Unlike unc-54 mutants, they respond to touch by strong contraction of the body-wall muscles followed promptly by relaxation. unc-93(el500sd) also confers a strong Egl defect, and a strong Exp (defecation) defect. Several Mac-d mutations do not cause Unc defects, but have Egl and Exp defects like unc-93. We have shown that all Mac-d mutations affecting egg-laying are resistant to serotonin and levamisole induction of egg-laying, suggesting post synaptic defects. Mac-h mutants are Egl-c and Dpy. The genes unc-58, unc-90, unc-105, and eat-12 (a.k.a. egl-l9) belong to this functional group. We have shown that the Dpy and Egl-c phenotypes of all Mac-h mutants are suppressed by mutations in unc-54, indicating that the Dpy and Egl-c phenotypes are caused by hyper-contracted body-wall and egg-laying muscle, respectively. All 15 of these Mac-d and Mac-h genes share genetic characteristics. The Mac-d and Mac-h phenotypes in each case are caused by semi-dominant mutations. In addition, of the eleven Mac genes for which loss-of-function mutations have been isolated, all but one of them have a grossly wild-type loss-of-function phenotype. We propose that the Mac-d and Mac-h genes function in the process of regulation of muscle excitation. We deem it unlikely that these genes are involved in the primary excitatory signal for muscle contraction, since l) most of these genes are not essential for muscle contraction, and 2) they affect multiple pharmacologically-distinct muscle types, suggesting that they encode components common to different muscles. We hypothesize that such components could be ion channels that modulate the basal excitability of muscle cells, regulatory signal transduction pathways that respond to modulatory neurotransmitters, or feedback or adaptation pathways. We have found that two additional genes, unc43 and unc-ll0, appear to act in the Mac process. Both are defined by semi-dominant mutations. unc-43 has a visible loss of-function phenotype, and unc-ll0 has one, grossly wild-type putative loss-of-function mutation. Therefore, they share the genetic characteristics of the Mac genes. However, we observed that unc-43(n498sd) appears Mac-h for body-wall muscle (suppressible by unc-54), but Mac-d for egg-laying and enteric muscles. The unc-43 loss-of-function mutations appear Mac-d for body-wall muscles, but are Mac-h for egg laying. Likewise, unc-ll0(el913sd) animals are Mac-d for body-wall muscles, but are Mac-h for egg laying. Therefore, these genes may positively regulate some muscle tissues and negatively regulate others. We have designated this phenotype Mac-m, for muscle activation-mixed. We speculate that unc-43 and unc-ll0 are good candidates for regulatory signal transduction pathway components. Further analysis of unc-43 is presented in the gazette by Reiner and Thomas. this issue. We'd like to thank and acknowledge the numerous workers in the worm field that have isolated and analyzed mutations in these loci, including (in alphabebical order): L. Avery, I. Greenwald, B. Horvitz, E. Jorgensen, R. Lee, J. Levin, E. Park, B. Schrank, D Thierry-Mieg, C. Trent, N. Tsung and B. Waterston.