The monoamine neurotransmitter transporters: structure, conformational changes and molecular gating.

Monoamine transporters are primary targets for the action of many psychoactive compounds including the most commonly used antidepressants and widely abused drugs, such as cocaine and amphetamine. Consequently, these transporters are the focus of continuous intensive research. Over the last couple of years, these efforts have resulted in significant progress both in our understanding of their role in drug abuse mechanisms and of the structural basis that underlies their capability as transporters to translocate their substrate across the plasma membrane. The aim of this review is to describe both the current awareness regarding the structural organization of the monoamine neurotransmitter transporters as well as the molecular mechanisms responsible for function, with specific emphasis on conformational changes and putative gating mechanisms.