Brain Plasma Membrane Monoamine Transporter in Health and Disease

Precise control of monoamine neurotransmitter levels in the central nervous system (CNS) is crucial for proper brain function. Dysfunctional monoamine signaling is associated with several neuropsychiatric and neurodegenerative disorders. The plasma membrane monoamine transporter (PMAT) is a new polyspecific organic cation transporter encoded by the SLC29A4 gene. Capable of transporting monoamine neurotransmitters with low affinity and high capacity, PMAT represents a major uptake₂ transporter in the brain. Broadly expressed in multiple brain regions, PMAT can complement the high-affinity, low-capacity monoamine uptake mediated by uptake₁ transporters, the serotonin, dopamine, and norepinephrine transporters (SERT, DAT, and NET, respectively). This chapter provides an overview of the molecular and functional characteristics of PMAT together with its regional and cell-type specific expression in the mammalian brain. The physiological functions of PMAT in brain monoamine homeostasis are evaluated in light of its unique transport kinetics and brain location, and in comparison with uptake₁ and other uptake₂ transporters (e.g., OCT3) along with corroborating experimental evidences. Lastly, the possibility of PMAT's involvement in brain pathophysiological processes, such as autism, depression, and Parkinson's disease, is discussed in the context of disease pathology and potential link to aberrant monoamine pathways.