The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro.

Abstract:

:The 5-HT(2A) serotonin receptor represents an important molecular target for atypical antipsychotic drugs and for most hallucinogens. In the mammalian cerebral cortex, 5-HT(2A) receptors are enriched in pyramidal neurons, within which 5-HT(2A) receptors are preferentially sorted to the apical dendrites. In primary cortical cultures, 5-HT(2A) 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-HT(2A) receptors to the dendrites of cortical pyramidal neurons in vitro. We constructed green fluorescent protein-tagged 5-HT(2A) 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-HT(2A) 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-HT(2A) receptors. We discovered that disruption of the PDZ-binding domain of the 5-HT(2A) receptor greatly attenuates the dendritic targeting of 5-HT(2A) receptors without inappropriately sorting 5-HT(2A) 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.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Xia Z,Hufeisen SJ,Gray JA,Roth BL

doi

10.1016/s0306-4522(03)00589-x

keywords:

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

907-20

issue

4

eissn

0306-4522

issn

1873-7544

pii

S030645220300589X

journal_volume

122

pub_type

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