Hh (red) catches a ride with lipophorin (green).


The Wingless (Wg) and Hedgehog (Hh) morphogens spread beween cells by catching a ride on lipoprotein particles, say Daniela Panáková, Hein Sprong, Christoph Thiele, Suzanne Eaton, and colleagues (Max Planck, Dresden, Germany).The group had earlier spotted unidentified intercellular signaling particles that they dubbed argosomes. Argosomes are now shown to be distinct from exosomes, a set of intercellular travelers derived from the exocytosis of multivesicular bodies. Instead, the argosome passengers Wg, Hh, and assorted glycophosphatidylinositol (GPI)-linked proteins colocalize with the fly protein lipophorin. This is the fly homologue of vertebrate lipoproteins, which scaffold low- and high-density lipoprotein (LDL and HDL) particles.

Getting rid of lipophorin with RNAi caused Wg and Hh to pile up near the cells that synthesize them in wing imaginal discs. The morphogens failed to spread as far as they normally do, although a nonargosome, nonexosome mechanism seems to ensure continued short-range spreading.

All these signaling proteins have lipid anchors that could insert into the glycolipid monolayer that surrounds lipoprotein particles, but how that insertion event might be controlled or promoted is unclear. When HDL particles pick up lipids from peripheral tissues they dock at scavenger receptors and rely on ABC transporters to spit lipids out of the cell. Eaton's group plans to test proteins that might carry out similar functions in delivering signaling proteins.

Lipoproteins may provide the morphogens with a vector that has just the right mobility; perhaps other proteins associated with the particles provide adhesive properties that ensure the particles do not spread throughout the body. The lipoprotein carriers might also “provide a link coordinating the morphogen gradient with nutritional status,” says Eaton. Starved flies grow up smaller, perhaps because they have less lipoprotein carriers to transport Wg and Hh morphogens such long distances.


Panáková, D., et al.