Internalised Material Fate-Degradation

If proteins are not retrieved from the endosomal compartment, then they are sent to the lysosome for degradation.

How does transport to the lysosome occur?

  • The early endosome invaginates to form multi vesicular bodies.
  • Proteins destined for degradation are sorted into these bodies. These proteins are made fully available to digestive enzymes which will degrade them.
  • Multi vesicular bodies gradually convert to late endosomes. This can be either by fusion with each other, or fusion with existing late endosomes.
  • The late endosome is competent for fusion with the lysosome-where degradation will occur.

What is the signal to sort proteins into multivesicular bodies?ESCRT Complex Machinery

Monoubiquitination

What does the sorting of ubiquitinated cargo depend on?

  • Ubiquitinated cargo is recognised by the enzyme HRS.
  • HRS is recruited to the early endosome, through its FYVE domain, which binds to PI3P. HRS forms a complex with a protein called STAM,
  • Ubiquitinated cargo can be sorted into flat Clathrin lattices. HRS can recruit Clathrin through its C terminal clathrin box motif (Clathrin binds to this).
  • From here cargo is fed into the ESCRT machinery.
  • The HRS/STAM complex recruits ESCRTI from the cytoplasm to the endosome. Here ESCRTI interacts with monoubiquitinated cargo.
  • ESCRTI activates ESCRTII. This initiates the oligomerisation of proteins, resulting in the formation of ESCRTIII.
  • The role of ESCRTIII is to concentrate multivesicular body cargo.

Image scanned in courtesey of Molecular Biology Of The cell. Alberts Fifth Edition- Fig 13-58. Copwright of Garland Science 2008