17-11-2014, 03:48
This info covers recycling of receptor control
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The Recycling and Degradation of G-protein Coupled Receptors
G-protein coupled receptors are not always present on the surface of the plasma membrane, instead these receptors are continually being taken into the cell to either be destroyed or to be recycled. Upon agonist binding to the receptor, the receptor becomes predisposed to internalisation. Internalisation involves the bound receptor being taken into the cell by endocytosis via clathrin coated pits which then bud off from the cell surface to form clathrin coated vesicle. Once in the vesicle the bound receptor is taken to endosomes - internal compartments of the cell - from there the receptors can either be recycled back to the plasma membrane, sequestration, or they can be directed to lysosomes where they will be degraded, downregulation.
G-protein coupled receptors have a constitutive rate of internalisation, that is specific to the particular type of receptor. The binding of agonist serves to increase the rate of endocytosed receptors. Even if the agonist dissociates from the receptor before internalisation can occur the receptor will still undergo endocytosis in the usual way. The amount of agonist that is endocytosed is dependent on the dissociation rate of the agonist from the receptor and the receptors natural constitutive endocytosic rate.
The rate of constitutive endocytosis of receptors depends on the number of surface receptors present. The rate will fall as internalisation reaches steady state. The proportion of receptors inside the cell at steady state is influenced by both the rates of endocytosis and recycling.
The process of sequestration is a dynamic one with the receptors constantly cycling between the plasma membrane and endosomes in the presence of the agonist. The process of downregulation involves the accelerated removal of receptor as well as a decrease in the rate of receptor synthesis
The different extents of recycling and degradation for different G-protein coupled receptors indicate that signals operate in early endosomes to determine the subsequent fate of the endocytosed receptor, with recycling to the plasma membrane being the default pathway. These signals have not yet been identified. It is possible that the activation state of the receptor when it reaches the endosome can determine its fate. Continued activation of the receptor in the endosome it is speculated will target the G-protein coupled receptor towards that of the lysosomal pathway. Therefore the fate of the receptor would depend on agonist affinity.
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Functional roles of short sequence motifs in the endocytosis of membrane receptors
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751658/
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Molecular Expressions
http://micro.magnet.fsu.edu/cells/endosomes/endosomes.html
http://micro.magnet.fsu.edu/micro/gallery.html
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Constitutive, agonist-accelerated, recycling and lysosomal degradation of GABA-B receptors in cortical neurons
http://www.sciencedirect.com/science/article/pii/S1044743108002480
----------------------------
The Recycling and Degradation of G-protein Coupled Receptors
G-protein coupled receptors are not always present on the surface of the plasma membrane, instead these receptors are continually being taken into the cell to either be destroyed or to be recycled. Upon agonist binding to the receptor, the receptor becomes predisposed to internalisation. Internalisation involves the bound receptor being taken into the cell by endocytosis via clathrin coated pits which then bud off from the cell surface to form clathrin coated vesicle. Once in the vesicle the bound receptor is taken to endosomes - internal compartments of the cell - from there the receptors can either be recycled back to the plasma membrane, sequestration, or they can be directed to lysosomes where they will be degraded, downregulation.
G-protein coupled receptors have a constitutive rate of internalisation, that is specific to the particular type of receptor. The binding of agonist serves to increase the rate of endocytosed receptors. Even if the agonist dissociates from the receptor before internalisation can occur the receptor will still undergo endocytosis in the usual way. The amount of agonist that is endocytosed is dependent on the dissociation rate of the agonist from the receptor and the receptors natural constitutive endocytosic rate.
The rate of constitutive endocytosis of receptors depends on the number of surface receptors present. The rate will fall as internalisation reaches steady state. The proportion of receptors inside the cell at steady state is influenced by both the rates of endocytosis and recycling.
The process of sequestration is a dynamic one with the receptors constantly cycling between the plasma membrane and endosomes in the presence of the agonist. The process of downregulation involves the accelerated removal of receptor as well as a decrease in the rate of receptor synthesis
The different extents of recycling and degradation for different G-protein coupled receptors indicate that signals operate in early endosomes to determine the subsequent fate of the endocytosed receptor, with recycling to the plasma membrane being the default pathway. These signals have not yet been identified. It is possible that the activation state of the receptor when it reaches the endosome can determine its fate. Continued activation of the receptor in the endosome it is speculated will target the G-protein coupled receptor towards that of the lysosomal pathway. Therefore the fate of the receptor would depend on agonist affinity.
------------------------------
Functional roles of short sequence motifs in the endocytosis of membrane receptors
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751658/
-------------------------------
Molecular Expressions
http://micro.magnet.fsu.edu/cells/endosomes/endosomes.html
http://micro.magnet.fsu.edu/micro/gallery.html
--------------------------------
Constitutive, agonist-accelerated, recycling and lysosomal degradation of GABA-B receptors in cortical neurons
http://www.sciencedirect.com/science/article/pii/S1044743108002480