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.