15 February 2003. Make that "blue cheese," a massive protein that is expressed in the CNS of Drosophila. In tomorrow’s Journal of Neuroscience, researchers at the Salk Institute, La Jolla, California, led by Michael McKeown of Brown University, Providence, Rhode Island, report that blue cheese mutations are involved in progressive neurodegeneration and the accumulation of protein aggregates.
Together with colleagues elsewhere, first author Kim Finley found blue cheese while working on the adjacent dissatisfaction gene on chromosome two of the fruit fly. Finley found that loss of blue cheese protein, or deletion of its first 200 amino acids, shortens the lifespan of the flies by about 40 percent. A similar fate befalls flies with insertions in blue cheese, which dramatically reduce its expression.
Blue cheese is a rather large protein, weighing in at over 380 KDa. It is expressed throughout the CNS, but not in muscle or fat tissue. The authors found it in the cytoplasm and axons of neurons, which is consistent, they write, with a role in vesicle transport or protein trafficking. Importantly, in blue cheese mutants, Finley et al. noticed that the CNS was peppered with protein aggregates that formed dark dots (and inspired the name). These turned out to contain ubiquitin and amyloid precursor-like protein and, though absent in young, day-old flies, become readily detectable by two weeks. The authors show that over a similar time frame, mutant flies exhibit signs of extensive neurodegeneration. The ommatidia of the compound eye, which have proven useful in studying fly neurodegeneration caused by mutant human proteins (see ARF related news story), begin to show signs of degeneration by day 10, and at two weeks have lost much of their distinctive morphology.
The exact function of BCHS is unknown, but several motifs in the protein offer clues. The BEACH motif, for example, is found in proteins regulating lysosomal trafficking, while the C-terminus end of the molecule contains a FYVE finger, which crops up in proteins regulating vesicle trafficking. Significantly, Finley report a high degree of conservation between Drosophila blue cheese and its human homolog ALFY, which was only recently described (Genbank accession number AF538685).-Tom Fagan.
Finley KD, Edeen PT, Cumming RC, Mardahl-Dumesnill MD, Taylor BJ, Rodriguez MH, Hwang CE, Benedetti M, McKeown M. Blue cheese mutations define a novel, conserved gene involved in progressive neural degeneration. J. Neurosci. 2003 February 15;23:1-11. Abstract
See press release.