Lecture 7 - Cross talk and compartmentalisation

Question 1

How is signalling compartmentalised?

Answer 1

1. Surface receptors are often ubiquitinylated following prolonged stimulation.
2. Monoubiquitinylation of receptors induces their endocytosis. The endosome often provides a second signalling platform with properties different from the plasma membrane.
3. Endocytosed ubiquitinylated receptors are sequestered into internal vesicles of a compartment called the multivesicular body.

Question 2

How are receptors down-regulated by sequestration?

Answer 2

If the release of the ligand is not promoted in the endosome, other measures are needed, since the endocytosed receptor is still signalling. These receptors are delivered to the compartment called the multivesicular body (MVB).

MVBs have internal vesicles formed from invaginations of their own limiting membrane. Once in the internal vesicle of the MVB, the receptor’s active cytosolic portion is sequestered from the cytosol. This physical separation stops signalling.

Receptors in MVBs can either be delivered to the lysosome for destruction, or can be recycled to the plasma membrane.