Gentle touch to the nematode body is sensed by five mechanosensory neurons called touch receptors. A multimeric channel composed of MEC-4 and MEC-10 degenerin channel subunits is expressed in the touch neurons and is needed for touch sensation. These channel subunits are thought to be the core elements of a mechanotransducing complex that includes other MEC proteins needed for touch sensation. Understanding how these proteins interact to facilitate touch transduction is of major interest in the field of mechanical signaling. Mutant, hyperactived variants of MEC-4 (MEC-4(A713V) =
mec-4(d)) can induce necrotic-like neurodegeneration of the touch receptor neurons, and thus
mec-4(d) has been of use as an initiating event for studying genetic requirements for neurodegeneration. Analogously substituted MEC-10 can also induce touch receptor degeneration. Of the dozen or so identified mec genes, only one,
mec-6, is esential for
mec-4(d)-induced neurodegeneration. Previously, we had reported that
mec-6 influences the stability of MEC-4/LacZ and MEC-4/GFP fusion proteins, provided they include most of the channel coding region. In the absence of
mec-6, very little if any tagged-MEC-4 protein is apparent. No effects on reporter activity are observed if transcriptional fusions that lack MEC-4 coding sequences are studied, suggesting that the loss of signal requires MEC-4 channel coding sequences.
mec-4 transcripts are not affected by
mec-6<i/> mutations. We suggest that
mec-6 is needed for the stability of the MEC-4 protein and postulate that
mec-6 suppresses neurodegeneration by dramatically lowering the concentration of MEC-4(d), thereby eliminating toxic ion influx into the touch receptor neurons.
mec-10(d)-induced neurodegeneration requires both
mec-6(+) and
mec-4(+) activity. However, it appears that the mechanism of
mec-6 suppression of
mec-10(d) is different from the case of
mec-4(d). We find that in the
mec-6 background, the expression levels of a MEC-10promoter/MEC-10/GFP (which encodes a chimeric protein including all but the last few MEC-10 amino acids followed by GFP) are not altered. Thus,
mec-6 does not appear to be required for MEC-10 stability although it is needed for MEC-4 stability. Since
mec-6 mutations appear to reduce/eliminate MEC-4 protein, we suggest that
mec-6</> suppression of
mec-10-induced neurodegeneration may occur via a mechanism analogous to suppression of
mec-10(d) by
mec-4(null) mutations. In this case, the MEC-10(d) subunit is still present, but cannot form a functional touch channel in the absence of sufficient MEC-4 subunits.