In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 17, No. 11 ( 2006-11), p. 4619-4631
Abstract:
PSD-95/Disc large/Zonula occludens 1 (PDZ) domain-containing proteins (PDZ proteins) play an important role in the targeting and the trafficking of transmembrane proteins. Our previous studies identified a set of PDZ proteins that interact with the C terminus of the serotonin 5-hydroxytryptamine (5-HT) 2C receptor. Here, we show that the prototypic scaffolding protein postsynaptic density-95 (PSD-95) and another membrane-associated guanylate kinase, MAGUK p55 subfamily member 3 (MPP3), oppositely regulate desensitization of the receptor response in both heterologous cells and mice cortical neurons in primary culture. PSD-95 increased desensitization of the 5-HT 2C receptor-mediated Ca 2+ response, whereas MPP3 prevented desensitization of the Ca 2+ response. The effects of the PDZ proteins on the desensitization of the Ca 2+ response were correlated with a differential regulation of cell surface expression of the receptor. Additional experiments were performed to assess how PDZ proteins globally modulate desensitization of the 5-HT 2C receptor response in neurons, by using a peptidyl mimetic of the 5-HT 2C receptor C terminus fused to the human immunodeficiency virus type-1 Tat protein transduction domain, which disrupts interaction between the 5-HT 2C receptor and PDZ proteins. Transduction of this peptide inhibitor into cultured cortical neurons increased the desensitization of the 5-HT 2C receptor-mediated Ca 2+ response. This indicates that, overall, interaction of 5-HT 2C receptors with PDZ proteins inhibits receptor desensitization in cortical neurons.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e06-03-0218
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2006
detail.hit.zdb_id:
1474922-1
SSG:
12
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