Sigma-2 receptor

The sigma-2 receptor (σ₂R) is a sigma receptor subtype that has been found highly expressed in malignant cancer cells, and is currently under investigation for its potential diagnostic and therapeutic uses. Originally, it was thought that the sigma receptors were a type of opiate receptor, due to its ability to bind ligands such as benzomorphans and PCP. Difficulties were found in distinguishing between the sigma-2 receptor and the NMDA receptors, though it is now known they are not the same entities, and have different distributions throughout the brain. The sigma-2 receptor in particular is more densely located in parts of the brain that are responsible for motor function and emotional response. It has been found to play a role in both hormone signaling and calcium signaling, in neuronal signaling, in cell proliferation and death, and in binding of antipsychotics. The position of the sigma-2 receptor has not yet been located on the human chromosome.

The sigma-2 receptor is a related protein located in the lipid raft that is most commonly associated with P450 proteins, and is coupled with the PGRMC1 complex, EGFR, mTOR, caspases, and various ion channels. It was previously thought to be the same as the NMDA receptor, is non-opioid, does not translocate, and unlike the sigma-1 receptor, has not been cloned. The sigma-2 receptor is found in several areas of the brain, including high densities in the cerebellum, motor cortex, and substantia nigra, though it shows no homology with other proteins present in brain tissue. It is also highly expressed in the lungs, liver, and kidneys.

The sigma-2 receptor takes part in a number of normal-function roles, including cell proliferation, and non-neuronal, and neuronal signaling. Much of sigma-2 receptor function relies on signaling cascades. The receptor's interaction with EGFR and PGRMC1 proteins allow for sigma-2 receptors to play diverse roles within cell through Ras, PLC, and PI3K singaling.

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