Worm Breeder's Gazette 8(3): 28
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.
The unc-52 allele su250 was described by Mackenzie et al. [Cell 15:751-762 (1978)] as a derivative of the e669 allele which, when homozygous, produced only a mildly uncoordinated phenotype as compared with the total paralysis produced by allele e669. Both sarcomere organization and myosin heavy chain B accumulation in su250 homozygotes were reported to be intermediate between wild-type and animals homozygous for more severe unc-52 alleles [Zengel & Epstein, PNAS 77:852-856 (1980)]. In our hands, strain HE250 unc-52(su250)II, obtained from CGC, shows a temperature-dependent paralyzed phenotype. When grown at 16 C, the worms are nearly wild-type in size and movement rate, paralysis sets in late in adulthood (late egg-laying uncoordination sets in earlier, becoming complete paralysis around the beginning of egg-laying. Worms grown at 20 C show an intermediate phenotype: partial paralysis is evident by early egg-laying and total paralysis occurs only late in adulthood. Outcross results with HE250 indicate that the ts phenotype does not result from extragenic suppression. Furthermore, when su250 is placed over an unc-52 null (e669) or a deficiency (jDf02), the animals are completely paralyzed even at 16 C. We infer that a single copy of the su250 allele produces insufficient functional gene product to sustain movement. Temperature shift experiments indicate that muscle function, rather than muscle morphogenesis alone, may be temperature-dependent. Adult su250 homozygotes grown at 16 C become noticeably impaired within 8 hrs. after an upshift to 25 C, and totally paralyzed in less than 240 hrs. Conversely, larvae or adults downshifted from 25 C to 16 C retain whatever degree of motor impairment they had at the time of the downshift. Thus, the phenotypic effect of high temperature is not reversible. We had previously reported (Worm Meetings, 1983) that unc-52 mutants are deficient in lysosomal cathepsin D. Both enzyme activity and cathepsin D protein (measured by quantitative immunoblots) are near- normal (50-75% of wt) in HE250 grown at 16 C, and are reduced (15-20% of wt) in paralyzed HE250 grown at 25 C. This matter is still under investigation, but we believe now that the cathepsin D deficiency is an indirect effect of underfeeding in paralyzed animals (see Clokey & Jacobson, this issue).