Worm Breeder's Gazette 13(4): 79 (October 1, 1994)
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 Biological Sciences, Columbia University
Dominant mutation in the genes deg-1 . mec-4 ,and mec-10 result in the degeneration of specific sets of neurons. These three genes encode for membrane proteins which belong to the degenerin gene family. Degenerin homologues in rat (alpha, beta, gamma rENaC) are components of an epithelial, amiloride-sensitive, sodium channel. mec-4 and mec-10 probably form a similar channel which is needed for the function of the touch receptor neurons. Cell degeneration, which is caused by these mutations, is probably a result of changes in the ion permeability of these channels, leading to osmotic imbalance and cell death. Thus, we believe that mutations that cause neuronal degeneration can lead to the identification of channel genes. We have been analyzing a number of degeneration-causing mutation. One of them deg-3 ( u662 )causes an uncoordinated phenotype and the degeneration of a small set of neurons. Because loss-of-function mutations in deg-3 produce no mutant phenotype, the gene may be non-essential. deg-3 encodes a homolgue of the a-7 nicotinic receptor, a vertebrate neuronal acetylcholine receptor which is highly permeable to Ca++ The degeneration-causing mutation in deg-3 affects the equivalent amino acid (in the second transmembrane domain) as is altered in the chick a-7 mutant (Galzi et al., Nature 359: 500-505 (1992)).Interestingly, the chick mutant receptor desensitizes slowly, a result consistent with the deg-3 ( u662 )phenotype. Thus, we believe that the deg-3 ( u662 )-causedcell death is a result of increased activity of the mutant channel. Support for this suggestion is provided by the partial suppression of the deg-3 ( u662 )phenotype which is seen in the presence of d-tuborcurarine. Although the vertebrate alpha-7 proteins can form homooligomer receptors in Xenopus oocytes, the nature of the receptor in vivo is unknown. We have identified two extragenic suppressor genes ( des-2 (II)and des-3 (III)that appear to be important for deg-3 function. Analysis of these suppressors may shed some light on the regulation of deg-3 function. The deg-3 ( u662 )mutation affects sensory neurons (touch receptor neurons and IL1 neurons) and interneurons (PVC, AVG), no motor neuron degeneration is seen. Expression of GFP, fused to the deg-3 upstream regions, is seen in the same position as the degenerating cells. Although we do not know the function of deg-3 ,the extensive overlap between cells that express deg-3 and cells that express the degenerins mec-4 , mec-10 ,and deg-1 is intriguing, and suggest an interaction between these two types of channels.