dopamine D4 receptor: biochemical and signalling properties

• Published in: Cellular and molecular life sciences : CMLS Vol. 67; no. 12; pp. 1971 - 1986
• Main Authors: Rondou, Pieter, Haegeman, Guy, Van Craenenbroeck, Kathleen
• Format: Journal Article
• Language: English
• Published: Basel Basel : SP Birkhäuser Verlag Basel 01.06.2010; SP Birkhäuser Verlag Basel; Springer Nature B.V
• Subjects: Animals; Attention Deficit Disorder with Hyperactivity; Attention Deficit Disorder with Hyperactivity - metabolism; Attention deficit hyperactivity disorder; Attention-deficit hyperactivity disorder (ADHD); Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Cell Biology; Cellular biology; Cricetinae; D4 receptor; dimerization; Dopamine; Dopamine - metabolism; Dopamine D4 receptors; Dopamine receptor-interacting protein (DRIP); dopamine receptors; G protein-coupled receptors; G-proteins; GPCR; GTP-Binding Proteins; GTP-Binding Proteins - metabolism; Internalization; Life Sciences; Memory; Mental disorders; metabolism; Molecular biology; motivation; Neurotransmitters; Polymorphism; Proteins; Proteins - metabolism; Receptor mechanisms; Receptors; Receptors, Dopamine D4; Receptors, Dopamine D4 - metabolism; Review; Reward; Schizophrenia; Schizophrenia - metabolism; Signal Transduction; Synaptic Transmission; Variable number of tandem repeats (VNTR); Attention-deficit hyperactivity disorder (ADHD); Variable number of tandem repeats (VNTR); Dopamine; Internalization; GPCR; D4 receptor; Dimerization; Dopamine receptor-interacting protein (DRIP)
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-010-0293-y

Dopamine is an important neurotransmitter that regulates several key functions in the brain, such as motor output, motivation and reward, learning and memory, and endocrine regulation. Dopamine does not mediate fast synaptic transmission, but rather modulates it by triggering slow-acting effects through the activation of dopamine receptors, which belong to the G-protein-coupled receptor superfamily. Besides activating different effectors through G-protein coupling, dopamine receptors also signal through interaction with a variety of proteins, collectively termed dopamine receptor-interacting proteins. We focus on the dopamine D4 receptor, which contains an important polymorphism in its third intracellular loop. This polymorphism has been the subject of numerous studies investigating links with several brain disorders, such as attention-deficit hyperactivity disorder and schizophrenia. We provide an overview of the structure, signalling properties and regulation of dopamine D4 receptors, and briefly discuss their physiological and pathophysiological role in the brain.