Receptor-mediated endocytosis

Receptor-mediated endocytosis (RME) is a process by which cells internalize molecules (endocytosis) into a cell by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.

Process
After binding of a ligand to plasma membrane spanning receptors, a signal is sent through the membrane, leading to clathrin coating the membrane, and formation of a membrane invagination. The receptor, its ligand, and anything nearby are then internalised in sub-micrometre sized clathrin-coated vesicles. Once internalised, the clathrin-coated vesicle uncoats (a pre-requisite for the vesicle to fuse with other membranes) and individual vesicles fuse to form the early endosome. Since the receptor is internalized with the ligand, the system is saturable and uptake will decline until receptors are recycled to the surface.

Function
The function of receptor-mediated endocytosis is diverse. Obviously it is widely used for the specific uptake of certain substances required by the cell (examples are the uptake of LDL via the LDL receptor or iron via transferrin). The role of receptor-mediated endocytosis is also well recognized in the downregulation of transmembrane signal transduction. The activated receptor becomes internalised and is transported to late endosomes and lysosomes for degradation. However, receptor-mediated endocytosis is also actively implicated in transducing signals from the cell periphery to the nucleus. This became apparent by the finding the association and formation of specific signaling complexes is required for the effective signaling of hormones (e.g. EGF). Additionally it has been proposed that the directed transport of active signaling complexes to the nucleus might be required to enable signaling as random diffusion is too slow (Howe, 2005) and mechanisms permanently downregulating incoming signals are strong enough to shutdown signaling completely without additional signals transducing mechanisms (Kholodenko, 2003).

Experiments
Using fluorescent dyes to stain the plasma membrane, it is possible to follow the internalization of plasma membrane fragments by microscopy.

Since the process is non-specific, the ligand can be a carrier for larger molecules. If the target cell has a known, specific pinocytotic receptor, drugs can be attached and will be internalized. Cancer cells appear to have an overexpression of folate receptors, so super-toxic, banned drugs may be re-examined due to far less side effects in non-target tissue.

Specific Properties

 * induction within minutes of exposure to excess ligand.
 * the formation of these vesicles is sensitive to inhibition by wortmannin
 * the initiation of vesicle formation can be delayed/inhibited by temperature variations