RGS9
Encyclopedia
Regulator of G-protein signalling 9, also known as RGS9, is a human gene
, which codes for a protein involved in regulation of signal transduction
inside cells. Members of the RGS family
, such as RGS9, are signaling proteins that suppress the activity of G protein
s by promoting their deactivation.[supplied by OMIM]
There are two splice isoforms of RGS9 with quite different properties and patterns of expression. RGS9-1 is mainly found in the eye and is involved in regulation of phototransduction in rod and cone cells of the retina
, while RGS9-2 is found in the brain, and regulates dopamine and opioid signaling in the basal ganglia
. This means that any targeting of RGS9 as a therapeutic target must be able to distinguish between these different tissue isoforms in order to avoid affecting vision.
RGS9-2 is of particular interest as the most important RGS protein involved in terminating signalling by the mu opioid receptor
(although RGS4
and RGS17
are also involved), and is thought to be important in the development of tolerance to opioid drugs. RGS9-deficient mice exhibit some motor and cognitive difficulties however, so inhibition of this protein is likely to cause similar side effects.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, which codes for a protein involved in regulation of signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
inside cells. Members of the RGS family
Regulator of G protein signalling
Regulators of G protein signalling are protein structural domains that activate GTPases for heterotrimeric G-protein alpha-subunits....
, such as RGS9, are signaling proteins that suppress the activity of G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
s by promoting their deactivation.[supplied by OMIM]
There are two splice isoforms of RGS9 with quite different properties and patterns of expression. RGS9-1 is mainly found in the eye and is involved in regulation of phototransduction in rod and cone cells of the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
, while RGS9-2 is found in the brain, and regulates dopamine and opioid signaling in the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
. This means that any targeting of RGS9 as a therapeutic target must be able to distinguish between these different tissue isoforms in order to avoid affecting vision.
RGS9-2 is of particular interest as the most important RGS protein involved in terminating signalling by the mu opioid receptor
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
(although RGS4
RGS4
Regulator of G protein signaling 4 or RGS4 is a protein which regulates G protein signaling. A number of studies associate the RGS4 gene with schizophrenia, while some fail to detect an association....
and RGS17
RGS17
Regulator of G-protein signaling 17 is a protein that in humans is encoded by the RGS17 gene.This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region...
are also involved), and is thought to be important in the development of tolerance to opioid drugs. RGS9-deficient mice exhibit some motor and cognitive difficulties however, so inhibition of this protein is likely to cause similar side effects.