It is concluded that in CSD neurons, (1) somatodendritic SERT supports ethanol attraction (2) axonal SERT specifies ethanol aversion, and (3) the effect of axonal SERT can override that of somatodendritic SERT. When globally re-expressed in serotonergic neurons, wild type SERT but not dSERT-R 599A restored ethanol preference after targeted expression in contralaterally projecting, serotonin-immunoreactive deuterocerebral (CSD) interneurons, while expression of wild type SERT caused ethanol aversion.
The possible physiological role of somatodendritic SERT was explored by comparing flies harboring wild type SERT and dSERT-R 599A in a behavioral paradigm for serotonin-modulated odor perception. Transgenic expression of the corresponding Drosophila mutant dSERT-R 599A led to its enrichment in the somatodendritic compartment of serotonergic neurons in the fly brain. This study introduced a point mutation into the RI-motif of human SERT causing confinement of the resulting (otherwise fully functional) hSERT-R 607A on the somatodendritic membrane of primary rat dorsal raphe neurons. Failure to engage SEC24C precludes axonal enrichment of SERT. The SERT C-terminus harbors a conserved RI-motif, which recruits SEC24C, a cargo receptor in the coatomer protein-II coat. Hence, the physiological role of somatodendritic SERT remains enigmatic. It has not been possible to restrict the distribution of SERT without affecting transporter function. SERT is not only delivered to axons but it is also present on the neuronal soma and on dendrites.
The serotonin transporter (SERT) regulates serotonergic neurotransmission by retrieving released serotonin and replenishing vesicular stores. NCBI link: EntrezGene, Nucleotide, Protein NCBI classification - Sodium:neurotransmitter symporter familyĬellular location - surface transmembrane Keywords - regulates serotonergic neurotransmission by retrieving released serotonin and replenishing vesicular stores, brain, CNS Serotonin transporter: Biological Overview
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