A discovery in yeast that has important implications for finding a cure for a devastating disease of nerve cell failures -- called familial dysautonomia (FD) -- has been made by Cornell University researchers.
They have found a gene that is a major player in determining the structural and functional asymmetry of cells -- known in modern biological parlance as cell polarity. The gene, called Elp1, is critical in regulating cell polarity, such as directing growth to the tip of a cell so that a "daughter" cell can "bud" off to divide, says Ruth Collins, assistant professor of molecular medicine in the College of Veterinary Medicine at Cornell.
"This discovery is exciting because it not only gives researchers new insight into basic mechanisms of cell growth and differentiation, but also provides critical insight into the pathogenesis of FD, which may arise in large part from a lack of fully developed neurons [nerve cells]," Collins says.
Her discovery is described in a paper in the March 18 issue of Molecular Cell (Vol. 17, No. 6). The paper is available online at http://www.molecule.org/ .
FD, which is manifested soon after birth and usually results in a life span of less than 30 years, is known to be caused by a genetic defect in a protein that is the human counterpart to the Elp1 gene in yeast.
"Not only is polarity important for normal cell function, but loss of polarity is associated with disease states, such as cancer, where reversal of the molecular pathway that creates cell polarity is one of the early steps in the progression to uncontrolled proliferation," Collins says.
The goal of Collins and two of her graduate students was to study how yeast establishes cell polarity by directing new growth to an area of the cell membrane where a "bud" can begin to grow into a daughter cell. The researchers looked at cells that were defective in cell growth and found several indications that suggested that the protein the Elp1 gene codes for -- called Elp1p -- plays an important role in directing cell polarity.
Previous research results have identified Elp1p as playing a different role -- that of gene expression, an activity that occurs in the nucleus of a cell, not out near the periphery of the cell where cell growth activity occurs.
To test their new hypothesis, the researchers devised an experiment that allowed proteins to enter the nucleus but then trapped them there to see if Elp1p had important roles both inside the nucleus for transcription as well as near the cell periphery for cell polarity and growth. They found that the protein, in fact, did not try to enter the nucleus but clearly stayed in the cytoplasm, the region of the cell outside the nucleus.