Abstract
The 5-HT2A serotonin receptor represents an important molecular target for atypical antipsychotic drugs and for most hallucinogens. In the mammalian cerebral cortex, 5-HT2A receptors are enriched in pyramidal neurons, within which 5-HT2A receptors are preferentially sorted to the apical dendrites. In primary cortical cultures, 5-HT2A receptors are sorted to dendrites and not found in the axons of pyramidal neurons. We identified a sorting motif that mediates the preferential targeting of 5-HT2A receptors to the dendrites of cortical pyramidal neurons in vitro. We constructed green fluorescent protein-tagged 5-HT2A receptors wherein potential sorting motifs were disrupted, and subsequently employed either the Semliki Forest virus or calcium phosphate for the transient expression of recombinant 5-HT2A receptors in cultured cortical pyramidal neurons. Using dual-labeling immunofluorescent confocal microscopy, we quantified the axonal and dendritic sorting patterns of endogenous and recombinant 5-HT2A receptors. We discovered that disruption of the PDZ-binding domain of the 5-HT2A receptor greatly attenuates the dendritic targeting of 5-HT2A receptors without inappropriately sorting 5-HT2A receptors to axons. The PDZ-binding domain is therefore a necessary signal for the preferential targeting of the 5-HT 2A receptor to the dendritic compartment of cultured cortical pyramidal neurons, the first such role ascribed to this protein-protein interaction motif of any G protein-coupled receptor.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 907-920 |
| Number of pages | 14 |
| Journal | Neuroscience |
| Volume | 122 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2003 |
| Externally published | Yes |
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Keywords
- Axon
- Dendrite
- G protein-coupled receptor
- GPCR
- Neuronal polarity
- Polarized protein sorting
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro. / Xia, Z.; Hufeisen, S. J.; Gray, John; Roth, B. L.
In: Neuroscience, Vol. 122, No. 4, 2003, p. 907-920.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro
AU - Xia, Z.
AU - Hufeisen, S. J.
AU - Gray, John
AU - Roth, B. L.
PY - 2003
Y1 - 2003
N2 - The 5-HT2A serotonin receptor represents an important molecular target for atypical antipsychotic drugs and for most hallucinogens. In the mammalian cerebral cortex, 5-HT2A receptors are enriched in pyramidal neurons, within which 5-HT2A receptors are preferentially sorted to the apical dendrites. In primary cortical cultures, 5-HT2A receptors are sorted to dendrites and not found in the axons of pyramidal neurons. We identified a sorting motif that mediates the preferential targeting of 5-HT2A receptors to the dendrites of cortical pyramidal neurons in vitro. We constructed green fluorescent protein-tagged 5-HT2A receptors wherein potential sorting motifs were disrupted, and subsequently employed either the Semliki Forest virus or calcium phosphate for the transient expression of recombinant 5-HT2A receptors in cultured cortical pyramidal neurons. Using dual-labeling immunofluorescent confocal microscopy, we quantified the axonal and dendritic sorting patterns of endogenous and recombinant 5-HT2A receptors. We discovered that disruption of the PDZ-binding domain of the 5-HT2A receptor greatly attenuates the dendritic targeting of 5-HT2A receptors without inappropriately sorting 5-HT2A receptors to axons. The PDZ-binding domain is therefore a necessary signal for the preferential targeting of the 5-HT 2A receptor to the dendritic compartment of cultured cortical pyramidal neurons, the first such role ascribed to this protein-protein interaction motif of any G protein-coupled receptor.
AB - The 5-HT2A serotonin receptor represents an important molecular target for atypical antipsychotic drugs and for most hallucinogens. In the mammalian cerebral cortex, 5-HT2A receptors are enriched in pyramidal neurons, within which 5-HT2A receptors are preferentially sorted to the apical dendrites. In primary cortical cultures, 5-HT2A receptors are sorted to dendrites and not found in the axons of pyramidal neurons. We identified a sorting motif that mediates the preferential targeting of 5-HT2A receptors to the dendrites of cortical pyramidal neurons in vitro. We constructed green fluorescent protein-tagged 5-HT2A receptors wherein potential sorting motifs were disrupted, and subsequently employed either the Semliki Forest virus or calcium phosphate for the transient expression of recombinant 5-HT2A receptors in cultured cortical pyramidal neurons. Using dual-labeling immunofluorescent confocal microscopy, we quantified the axonal and dendritic sorting patterns of endogenous and recombinant 5-HT2A receptors. We discovered that disruption of the PDZ-binding domain of the 5-HT2A receptor greatly attenuates the dendritic targeting of 5-HT2A receptors without inappropriately sorting 5-HT2A receptors to axons. The PDZ-binding domain is therefore a necessary signal for the preferential targeting of the 5-HT 2A receptor to the dendritic compartment of cultured cortical pyramidal neurons, the first such role ascribed to this protein-protein interaction motif of any G protein-coupled receptor.
KW - Axon
KW - Dendrite
KW - G protein-coupled receptor
KW - GPCR
KW - Neuronal polarity
KW - Polarized protein sorting
UR - http://www.scopus.com/inward/record.url?scp=0344441294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344441294&partnerID=8YFLogxK
U2 - 10.1016/S0306-4522(03)00589-X
DO - 10.1016/S0306-4522(03)00589-X
M3 - Article
VL - 122
SP - 907
EP - 920
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 4
ER -