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Receptor-mediated endocytosis (RME), also called clathrin-dependent endocytosis, is a process by which cells absorb molecules (endocytosis) by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being absorbed.
After the binding of a ligand to plasma membrane-spanning receptors, a signal is sent through the membrane, leading to membrane coating, and formation of a membrane invagination. The receptor and its ligand are then opsonized in clathrin-coated vesicles. Once opsonized, 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.
The function of receptor-mediated endocytosis is diverse. It is widely used for the specific uptake of certain substances required by the cell (examples include 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 when it was found that 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 and mechanisms permanently downregulating incoming signals are strong enough to shutdown signaling completely without additional signals transducing mechanisms.
Using fluorescent dyes to stain the plasma membrane, it is possible to follow the internalization of plasma membrane fragments by microscopy.
- 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
- Non-specific, adsorptive pinocytosis
- Bulk endocytosis
- 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 (1): 43. PMC 1276819. PMID 16236165. doi:10.1186/1742-4682-2-43. 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 (Pt 12): 2073–82. PMID 12756289. doi:10.1242/jeb.00298. 206, 2073-2082.
- CytoChemistry.net- A lecture on RME with some nice pictures
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