Published online 3 January 2002. doi:10.1083/jcb1561rr4
© The Rockefeller University Press,
0021-9525/2002/1/11-a $5.00
The Journal of Cell Biology, Volume 156, Number 1, January 7, 2002 11-a-11
The good side of a maligned protein
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ß-secretase and APP colocalize in mouse sciatic nerve.
Goldstein/Macmillan
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Scientists have discovered a new function for amyloid precursor protein (APP), a protein linked to Alzheimer's disease. The finding may reveal how APP gets mixed up with the enzymes that make it go bad.APP has an evil reputation. The ß and 
secretases transform it into amyloid-ß peptide, a component of the plaques that riddle the brain in Alzheimer's disease. Previous work by Larry Goldstein (Univesity of California, San Diego, CA) and coworkers suggested that APP normally links to kinesin, a protein that tows vesicles and organelles around the cell. Now Goldstein and colleagues have bolstered this hypothesis by examining neurons from APP-deficient mice. They found that the protein cargoes usually transported by kinesin couldn't travel along the axon, whereas proteins not hauled by kinesin could. The researchers conclude that APP serves as a trailer hitch, coupling the membrane of a vesicle or organelle to kinesin. It turns out that two of the proteins moved by kinesin are the secretases, so APP and the enzymes that transform it into amyloid-ß ride around together. Vesicles may therefore be the place where APP turns into amyloid-ß, Goldstein says.
"The results may give us some clues as to why neurons die in the disease," says Goldstein. One possibility is that increased cleavage of APP, perhaps triggered by an injury, may foul up transport along the axons—in effect creating a fatal intracellular traffic jam. 
Reference:
Kamal, A., et al. 2001. Nature. 414:643–648.[Medline]
Mitch Leslie
mleslie{at}cybermesa.com
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