Eaton first observed the structures when she was studying apical–basal sorting of proteins that have glycophosphatidylinositol (gpi) tails. “It was this completely random observation several years ago,” she says. “When we saw this we just dropped working on apical–basal sorting.”
What she saw were clusters of her labeled protein, a fusion of GFP to a gpi tail, in nonexpressing tissue. The signaling molecule wingless was found in a similar pattern, with both molecules forming gradients that drop with increasing distance from the domain of expression (although the gradient is steeper for wingless).
Eaton believes that lipid carriers are responsible because GFP lacks a surface receptor that could concentrate any proteinthat was somehow solubilized. She also found that a fluorescent fusion protein associated with the cytoplasmic face of the membrane turned up in the same pattern.
Argosomes might allow the cell to cluster signaling molecules into concentrated packages, and to pair them with other regulatory molecules. In addition, argosomes move proteins rapidly inside cells, although this movement appears to be undirected. The failure to see argosomes outside of cells may reflect an inability to detect smaller protein clusters.
Eaton and colleagues suggest two potential mechanisms for creating argosomes. One possibility involves the engulfment by one cell of protrusions formed by another cell, as seen during the spread of Listeria bacteria. Alternatively, proteins such as wingless may first be exported from the cell, bind to a gpi-linked heparan sulfate proteoglycan, and be brought back into the cell by endocytosis. Then membrane vesicles would bud internally into the endosomes to form multivesicular bodies, which have been noted before as a site of wingless localization. Fusion of the multivesicular bodies with the plasma membrane would release the argosomes. ▪