2000 West Coast Worm Meeting abstract 72
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University of Utah, SLC UT 84112
We cloned unc-70 and found that it encodes the C. elegans homolog of beta-spectrin, an essential component of the membrane skeleton.1 The membrane skeleton is a protein mesh that binds to the plasma membrane and that interacts with a large number of membrane and cytosolic proteins. It has been proposed that the membrane skeleton functions to support the plasma membrane or to generate cell polarity. However, we found that null mutations in unc-70 do not result in general membrane or polarity defects. unc-70 null animals have a severe paralyzed, dumpy phenotype. By analyzing this phenotype we have identified at least three specific processes that are perturbed by loss of beta-spectrin. First, we found defects in axonal morphology, suggesting that the membrane skeleton plays an essential role in neuronal development. We suspect that loss of beta-spectrin may specifically affect growth cone motility and are conducting time-lapse studies of unc-70 growth cones to test this hypothesis. Second, we found that loss of beta-spectrin causes defects in the myofilament attachment structures of body wall muscle (dense bodies and M lines). We are using a panel of antibodies against components of these structures to understand how the membrane skeleton functions in muscle. Finally, the membrane skeleton appears to function in synaptic transmission. We found that rare dominant alleles of unc-70 do not exhibit the null phenotypes described above; rather, they have abnormally high levels of neurotransmission. Preliminary evidence suggests that synaptic vesicles are mislocalized within the nerve terminal of these mutants. We are analyzing the synaptic ultrastructure of these mutants, and using electrophysiology to relate structural defects to possible functional roles for beta-spectrin in nerve terminals.
1. Hammarlund, M. et al., J. Cell Biol., 149(4), 2000.