USP8: The Unexpected Hero in Endosome Maturation

Endosomes are like tiny sorting centers in our cells, and they need to go through some steps to mature properly. This process is like a relay race, where one runner (Rab5) hands over the baton to another (Rab7). But how this handover happens is a mystery. Meet USP8, a protease that cuts off tiny tags called ubiquitins from proteins. It turns out USP8 has a special job in this relay race. It's recruited to the start of the race by Rabex5, a helper that activates Rab5. When USP8 jumps in, Rabex5 steps back, and a new helper, SAND-1/Mon1, joins to activate Rab7.Without USP8, things get messy. Rab5 keeps going strong, but Rab7 takes a backseat. Early endosomes (EEs) grow big and filled with small bubbles. Meanwhile, lysosomes, which are like the recycling centers, aren't fully formed. It's like the relay race never ends, with Rab5 still holding the baton and Rab7 sitting on the sidelines. This shows that USP8 is more than just a protease. It's a key player in this cellular relay race, making sure the baton gets passed smoothly.