Receptor-mediated endocytosis

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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.

1 Process
2 Function
3 Experiments
4 Specific Properties
5 References
6 External links

[edit] 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 and its ligand 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.

[edit] 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).

[edit] Experiments

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

[edit] 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

[edit] References

Alberts, Bruce; et. al. (2004). Essential Cell Biology, 2nd Edition (in English), New York, NY: Garland Science. ISBN 0-8153-3480-X. Retrieved on December 2006.
Howe, Charles L. (2005). "Modeling the Signaling Endosome Hypothesis: Why a Drive to the Nucleus Is Better Than a (Random) Walk". Theor. Biol. Med. Mod. 2:43.
Kholodenko, Boris N. (2003). "Four-Dimensional Organisation of Protein Kinase Signaling Cascades: the Roles of Diffusion, Endocytosis and Molecular Motors". J. Exp. Biol. 206, 2073-2082.