Psychosine receptor (IPR005464)
Short name: Psych_rcpt
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- Psychosine receptor (IPR005464)
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [PMID: 12679517]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [PMID: 8170923]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 16753280]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [PMID: 12679517]. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [PMID: 23020293].
The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [PMID: 2111655, PMID: 2830256, PMID: 8386361].
Psychosine is a glycosphingolipid implicated in the pathology of globoid cell leukodystrophy (GLD), a hereditary metabolic disorder that results from the absence of the enzyme galactosyl ceramide. This deficiency results in the accumulation of psychosine in the brain, leading to apoptosis of oligodendrocytes, progressive demyelination and the existence of large, multinuclear cells (globoid cells) derived from microglia [PMID: 11309421].
The molecular mechanism by which these toxic effects might be mediated has recently been elucidated by the identification of TDAG8, an orphan G protein-coupled receptor, as a receptor for psychosine [PMID: 11309421]. TDAG8 is expressed at high levels in the spleen, peripheral blood leukocytes, lymph nodes and lung. Activation of the receptor in RH7777 hepatoma cells by psychosine and related lysoglycolipids results in a pertussis toxin- insensitive inhibition of forskolin-induced cAMP accummulation, possibly through coupling to Gz proteins [PMID: 11309421].
- PR01649 (PSYCHOSINER)