Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb
metabolites,
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s,
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s – and in some cases
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
es – by the inward budding of the
plasma membrane (
invagination). This process forms
vesicles
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
containing the absorbed substances and is strictly mediated by
receptors on the surface of the cell. Only the receptor-specific substances can enter the cell through this process.
Process
Although receptors and their
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elect ...
s can be brought into the cell through a few mechanisms (e.g.
caveolin
In molecular biology, caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis. Caveolins may act as scaffolding proteins within caveolar ...
and
lipid raft),
clathrin-mediated endocytosis remains the best studied. Clathrin-mediated endocytosis of many receptor types begins with the ligands binding to receptors on the cell plasma membrane. The ligand and receptor will then recruit adaptor proteins and clathrin
triskelion
A triskelion or triskeles is an ancient motif consisting of a triple spiral exhibiting rotational symmetry.
The spiral design can be based on interlocking Archimedean spirals, or represent three bent human legs. It is found in artefacts o ...
s to the plasma membrane around where invagination will take place. Invagination of the plasma membrane then occurs, forming a clathrin-coated pit.
Other receptors can nucleate a clathrin-coated pit allowing formation around the receptor. A mature pit will be cleaved from the plasma membrane through the use of membrane-binding and fission proteins such as
dynamin
Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamin is part of the "dynamin superfamily", which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA1, mitofusins, and GBPs. Members of the dynamin fami ...
(as well as other
BAR domain proteins), forming a clathrin-coated vesicle that then uncoats of clathrin and typically fuses to a sorting
endosome. Once fused, the endocytosed cargo (receptor and/or ligand) can then be sorted to
lysosomal, recycling, or other trafficking pathways.
Function
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
The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor t ...
or iron via
transferrin
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encod ...
). The role of receptor-mediated endocytosis is well recognized up take downregulation of transmembrane signal transduction but can also promote sustained 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 via clathrin-mediated endocytosis 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, due to the fact that random
diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical ...
is too slow, and mechanisms permanently downregulating incoming signals are strong enough to shut down signaling completely without additional signal-transducing mechanisms.
Experiments
Using fluorescent or EM visible dyes to tag specific molecules in living cells, it is possible to follow the internalization of cargo molecules and the evolution of a clathrin-coated pit by fluorescence microscopy and immuno electron 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
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
, drugs can be attached and will be internalized.
To achieve internalisation of
nanoparticles into cells, such as
T cells,
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
can be used to target the nanoparticles to specific receptors on the cell surface (such as
CCR5). This is one method of improving drug delivery to immune cells.
The development of
photoswitchable peptide inhibitors of
protein-protein interactions involved in
clathrin-mediated endocytosis (Traffic Lights peptides) and photoswitchable small molecule inhibitors of
dynamin
Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamin is part of the "dynamin superfamily", which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA1, mitofusins, and GBPs. Members of the dynamin fami ...
(Dynazos)
has been reported. These
photopharmacological compounds allow spatiotemporal control of the endocytosis with light.
Characteristics
* Induction within minutes of exposure to excess ligand.
* The formation of these vesicles is sensitive to inhibition by
wortmannin
Wortmannin, a steroid metabolite of the fungi ''Penicillium funiculosum'', '' Talaromyces wortmannii'', is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an ''in vitro'' inhibitory concentration (''IC''50) of a ...
* The initiation of vesicle formation can be delayed/inhibited by temperature variations
See also
*
Non-specific, adsorptive pinocytosis
*
Pinocytosis
*
Phagocytosis
*
Viropexis Viropexis is the process by which different classes of viruses—particularly picornaviruses and papovaviruses—enter the host cell in which they will be able to replicate. The hydrophobic structures of the capsid proteins may be exposed after v ...
*
Bulk endocytosis Bulk endocytosis refers to a form of endocytosis of synaptic vesicles at Chemical synapse, nerve terminals. In bulk endocytosis, compared to clathrin-mediated endocytosis, a larger area of presynaptic Cell membrane, plasma membrane is internalised ...
*
Endocytosis
References
External links
CytoChemistry.net A lecture on RME with some nice pictures
{{DEFAULTSORT:Receptor-Mediated Endocytosis
Cellular processes