An endosomal switchboard

Studies on the internalization of signaling receptors generally suggest that receptor endocytosis attenuates signaling. On page 1239, Hayes et al. turn this concept on its head, showing that inhibiting endocytosis actually impairs TGFβ receptor signaling. The findings suggest that endosomes may in fact serve as specialized signaling compartments that amplify and propagate certain types of cellular signals.

The authors found that the endogenous TGFβ receptor in cultured cells localizes to endosomes containing the early endosomal marker EEA1. SARA, a soluble cytoplasmic protein required for TGFβ function, is found almost exclusively in the same EEA1-enriched endosomes. Disrupting TGFβ receptor endocytosis impairs downstream signaling events normally mediated by the receptor. This result is reminiscent of the disruption of antiapoptotic signaling recently noted in cells that lack clathrin function (Wettey, F.R., et al. 2002. Science 297:1521–1525).

This is the first...