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.

Neuronal Degeneration Caused by Mutations of an Acetylcholine Receptor in C. elegans.

Millet Treinin, Marty Chalfie

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
  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
  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