Role of Dimerization in Dopamine D4 Receptor Biogenesis

Author(s): Kathleen Van Craenenbroeck, Dasiel O. Borroto-Escuela, Kamila Skieterska, Jolien Duchou, Wilber Romero-Fernandez, Kjell Fuxe

Journal Name: Current Protein & Peptide Science

Volume 15 , Issue 7 , 2014


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Abstract:

Dopamine receptors are G protein-coupled receptors critically involved in locomotion, reward, and cognitive processes. Export of dopamine receptors to the plasma membrane is thought to follow the default secretory pathway, whereby proteins travel from the endoplasmatic reticulum (ER), through the Golgi apparatus, to arrive at the cell surface. Several observations indicate that trafficking from the ER to the plasma membrane is tightly regulated, and that correct folding in the ER acts as a bottle neck to the maturation of the dopamine D4 receptors. The dopamine D4 receptor is an interesting receptor since it has a polymorphic region in its third intracellular loop, resulting in receptor isoforms of varying length and amino acid composition. Correct folding is enhanced by: (1) interaction with specific proteins, such as ER resident chaperones, (2) interaction with pharmacological chaperones, for example, ligands that are membrane permeable and can bind to the receptor in the ER, and (3) receptor dimerization; the assembly of multisubunit proteins into a quaternary structure is started in the ER before cell surface delivery, which helps in correct folding and subsequent expression. These interactions help the process of GPCR folding, but more importantly they ensure that only properly folded proteins proceed from the ER to the trans-Golgi network. In this review we will mainly focus on the role of receptor dimerization in dopamine D4 receptor maturation.

Keywords: ADHD, chaperone, dimerization, dopamine D2 receptor, dopamine D4 receptor, endoplasmic reticulum, G proteincoupled receptors, polymorphic variants.

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Article Details

VOLUME: 15
ISSUE: 7
Year: 2014
Published on: 16 September, 2014
Page: [659 - 665]
Pages: 7
DOI: 10.2174/1389203715666140901110256
Price: $65

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