Reverse transport

Transporter reversal or reverse transport is a phenomenon in which the substrates of a membrane transporter are moved in the opposite direction to that of their typical movement by the transporter. Transporter reversal typically occurs when membrane transport proteins undergoes phosphorylation by a particular protein kinase, which is an enzyme that adds a phosphate group to proteins.

The primary function of most neurotransmitter transporters is to facilitate neurotransmitter reuptake (i.e., the reabsorption of neurotransmitters by the cell which released them). During neurotransmitter reuptake, these transporter will move specific types of neurotransmitters from the extracellular space into the cytosol of a neuron or glial cell. When these transporters operate in reverse, they produce neurotransmitter efflux (i.e., the movement of neurotransmitters from the cytosol to the extracellular space). In neurons, transporter reversal facilitates the release of neurotransmitters into the synaptic cleft, which subsequently increases the binding of these neurotransmitters at their associated neurotransmitter receptors. For example, many monoamine releasing agents produce monoamine efflux (i.e., the release of monoamine neurotransmitters from neurons into the synaptic cleft) by triggering reverse transport at vesicular monoamine transporters (specifically VMAT1 and VMAT2) and other monoamine transporters that are located along the plasma membrane of neurons (specifically, DAT, NET, and SERT).

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