Disease relevance of mec-4

• Here we report on intragenic mec-4 mutations identified in a screen for suppressors of mec-4(d)-induced necrosis, with a focus on detailed characterization of allele bz2 that has the distinctive phenotype of inducing dramatic neuronal swelling without being fully penetrant for toxicity [1].

High impact information on mec-4

• In the nematode Caenorhabditis elegans, gain-of-function mutations in the degenerin genes mec-4 and mec-10 (denoted mec-4(d) and mec-10(d), respectively) cause degeneration of the touch cells [2].
• The gene encoding this rat sodium channel subunit shares significant sequence similarity with mec-4 and deg-1, members of a family of Caenorhabditis elegans genes involved in sensory touch transduction and, when mutated, neuronal degeneration [3].
• Null mutations in the DEG/ENaC gene mec-4 and in the accessory ion channel subunit genes mec-2 and mec-6 eliminated MRCs [4].
• Screens for additional dominant enhancers of mec-4 and mec-5 yielded mutations in previously known genes [5].
• Here we show that UNC-86::MEC-3 hetero-oligomer-binding sites are also found in the promoters of two presumed targets of mec-3, the mec-4 and mec-7 genes, that are necessary for the function of the touch cells [6].

Biological context of mec-4

• RESULTS: We now demonstrate that a missense change in a predicted extracellular region of the proteins encoded by deg-1 and mec-4 causes cell death similar to that caused by the dominant mutations [7].
• The channel subunits have significant homologies with the Caenorhabditis elegans mec-4, mec-10 and deg-1 genes, which are involved in control of cell volume and mecanotransduction [8].
• The results of gene dosage and dominance tests suggest that the mec-4(+) gene product, which is required for wild-type microtubule cell function, is altered by the e 1611 mutation into a novel product that kills the microtubule cells [9].

Other interactions of mec-4

• With deg-1, another C. elegans gene that can mutate to induce neuronal degeneration and that is similar in sequence, mec-4 defines a new gene family [10].

Analytical, diagnostic and therapeutic context of mec-4

• Immunoprecipitation of in vitro translated mec-4 protein with domain-specific anti-MEC-4 antibodies and in vivo characterization of a series of mec-4lacZ fusion proteins both support the hypothesis that MEC-4 crosses the membrane twice [11].
• Comparative sequence analysis of C. elegans and Caenorhabditis briggsae mec-4 genes was used to initiate molecular studies that establish MEC-4 as a 768-amino acid protein that includes two hydrophobic domains theoretically capable of spanning a lipid bilayer [11].

References