Ubiquitin (blue) builds up on receptors in endosomes (red) when AMSH (green) is mutated.
Activated internalized receptors are tagged with ubiquitin for sorting to lysosomes from endosomes rather than recycling back to the plasma membrane. Until now, ubiquitin was thought to be removed only just before the receptor's destruction to preserve cellular ubiquitin pools. But the new work shows that an endosomal enzyme called AMSH acts early enough to prevent receptor degradation.
AMSH saves receptors by removing the destruction tags. In vitro, AMSH removed ubiquitin from substrates such as the EGF receptor. In cells, a dominant-negative AMSH mutant caused an accumulation of ubiquitin at endosomes.
More ubiquitination means more destruction. In...
