Tuesday, May 14, 2024
5/14/2024
DESCRIPTION (provided by applicant): Muscle and nerve cell functions are largely due to the function of transmembrane ion channels. Mutations in ion channel genes can lead to uncoordinated movement, or to the loss or attenuation of particular behaviors. The role of a particular potassium channel and its regulators in coordinating muscle contraction and in executing a set of ritualized male mating behaviors of the worm, Caenorhabditis elegans, will be studied. In C. elegans, a set of four genes, including sup-9 and unc-93, is known to encode a potassium channel and its putative regulators. Gain-of-function mutations in either of these genes lead to paralysis; loss-of-function alleles cause the animal no harm. Gain-of-function mutations in one gene can be suppressed by loss-of-function alleles in another of these four genes, presumably by eliminating channel function. We have isolated a set of unique sup-9 alleles that suppress the paralysis conferred by a gain-of-function allele of unc-93, but that leave male worms incapable of mating. The SUP-9 channel is found in the membrane of all muscle cell types but also in a small subset of neurons. We intend to fully characterize the mating defect conferred by these alleles and to determine whether the defect is due to aberrant channel activity in muscle cells or in neurons. We also will determine how the role of the SUP-9 channel compares with that of other K+ channels. We recently isolated a worm strain that appears to contain a spontaneous mutation that suppresses only one male-specific aspect of the unc-93 gain-of-function phenotype, indicating either that the SUP-9 channel is regulated differently in different tissues or that unc-93 is involved in more than one signaling pathway. We propose to map the location of this suppressor and undertake its molecular characterization. This research will be an important contribution to our understanding of the role of potassium channel function and regulation and the role of K+ channels in coordinating animal behavior. Lastly, this research will help delineate the connections between motility, functions of particular muscle cells, and organismal behavior.
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