Oligomerization of neurotransmitter transporters: a ticket from the endoplasmic reticulum to the plasma membrane

Abstract

Cellular localization of neurotransmitter transporters is important for the precise control of synaptic transmission. By removing the neurotransmitters from the synaptic cleft, these transporters terminate signalling and affect duration and intensity of neurotransmission. Thus, a lot of work has been invested in the determination of the cellular compartment to which neurotransmitter transporters localize. In particular, the polarized distribution has received substantial attention. However, trafficking of transporters in the early secretory pathway has been largely ignored. Oligomer formation is a prerequisite for newly formed transporters to pass the stringent quality control mechanisms of the endoplasmic reticulum (ER), and this quaternary structure is also the preferred state which transporters reside in at the plasma membrane. Only properly assembled transporters are able to recruit the coatomer coat proteins that are needed for ER-to-Golgi trafficking. In this review, we will start with a brief description on transporter oligomerization that underlies ER-to-Golgi trafficking, followed by an introduction to ER-to-Golgi trafficking of neurotransmitter transporters. Finally, we will discuss the importance of oligomer formation for the pharmacological action of the illicitly used amphetamines and its derivatives.