Neurotransmitter Transport

The Molecular Machinery of Mood Swings

Science's STKE  11 Sep 2007:
Vol. 2007, Issue 403, pp. tw326
DOI: 10.1126/stke.4032007tw326

The action of monoamine neurotransmitters that serve as signaling molecules in mood and motivation begins when they are released from the presynaptic nerve terminal and ends when they are transported from the extracellular space back into the cytoplasm via dedicated sodium-dependent plasma membrane transporters. Zhou et al.describe the crystal structure of a bacterial homolog (LeuT) of the mammalian monoamine transporters in complex with its substrate (leucine) and an inhibitor of norepinephrine transport (the antidepressant desipramine). On the basis of homology modeling of the human transporters for serotonin, norepinephrine, and dopamine (hSERT, hNET, and hDAT), they construct mutants of hSERT and hDAT and show that these exhibit the predicted sensitivity of serotonin and dopamine uptake to desipramine inhibition.

Z. Zhou, J. Zhen, N. K. Karpowich, R. M. Goetz, C. J. Law, M. E. A. Reith, D.-N. Wang, LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake. Science 317, 1390-1393 (2007). [Abstract] [Full Text]