Abstract
The dopamine transporter utilizes the transmembrane sodium gradient to mediate reuptake of dopamine from the extracellular space. The dopamine transporter can form dimers and possibly also higher order structures in the plasma membrane, and this oligomerization has been implicated in both trafficking and transport. However, we still do not fully understand its biological importance. A study by Sorkina et al. now describes a series of small molecules that link transporter conformation to oligomerization and endocytosis, providing an interesting step forward in an intricate dance.
Highlights
“It takes two to tango” is a classical cliché that was already suggested many years ago to describe the putative importance of dimerization of dopamine transporter (DAT) and the two other monoamine transporters, SERT and NET [3]
The data are somewhat blurry as in vivo studies suggested that repeated administration of metamphetamine to mice increases DAT oligomerization [8], whereas in vitro studies rather have supported that amphetamines disperse oligomer formation [9]
The authors suspected that these observations were independent of ACK1 activity, but because ACK1 has been proposed to regulate DAT endocytosis, they could not be sure without more specific compounds
Summary
“It takes two to tango” is a classical cliché that was already suggested many years ago to describe the putative importance of dimerization of DAT and the two other monoamine transporters, SERT and NET [3]. Of particular interest in relation to the study by Sorkina et al [7], it has been shown that ligands targeting DAT, like amphetamines, can affect oligomerization. The data are somewhat blurry as in vivo studies suggested that repeated administration of metamphetamine to mice increases DAT oligomerization [8], whereas in vitro studies rather have supported that amphetamines disperse oligomer formation [9].
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