The fusion (right) of early endosomes (left) is inhibited by Hrs.

Endocytosed proteins come together in the early endosome to be sorted to different locations. Some endosome fusion is needed to promote this mixing, but the process must be regulated both to stop the formation of one giant early endosome and to promote eventual sorting. Now, Sun et al. (page 125) have developed a clever assay for studying homotypic endosome fusion and used it to uncover a surprising new fusion inhibitor activity for an early endosome protein called Hrs.The authors allowed different populations of HeLa cells to endocytose EGF linked to one of two different fluorophores, and then isolated pools of endosomes or lysosomes from the cells. When the isolated organelles were allowed to fuse in cell-free reactions, the mixing of their contents caused fluorescence resonance energy transfer between the two fluorophores, providing...

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