4.6 Article

Modulation of 5-HT3 receptor desensitization by the light chain of microtubule-associated protein 1B expressed in HEK 293 cells

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JOURNAL OF PHYSIOLOGY-LONDON
卷 586, 期 3, 页码 751-762

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BLACKWELL PUBLISHING
DOI: 10.1113/jphysiol.2007.136440

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  1. Intramural NIH HHS Funding Source: Medline

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Regulation of ligand-gated ion channel (LGIC) function and trafficking by cytoskeleton proteins has been the topic of recent research. Here, we report that the light chain (LC1) of microtubule-associated protein 1B (MAP1B) specifically interacted with the 5-HT3A receptor, a predominant serotonin-gated ion channel in the brain. LCI and 5-HT3A receptors were colocalized in central neurons and in HEK 293 cells expressing 5-HT3A receptors. LC1 reduced the steady-state density of 5-HT3A receptors at the membrane surface of HEK 293 cells and significantly accelerated receptor desensitization time constants from 3.8 +/- 0.3 s to 0.8 +/- 0.1 s. However, LC1 did not significantly alter agonist binding affinity and single-channel conductance of 5-HT3A receptors. On the other hand, application of specific LC1 antisense oligonucleotides and nocodazole, a microtubule disruptor, significantly prolonged the desensitization time of the recombinant and native neuronal 5-HT3 receptors by 3- to 6-fold. This kinetic change induced by nocodazole was completely rescued by addition of LC1 but not GABA(A) receptor-associated protein (GABARAP), suggesting that LC1 can specifically interact with 5-HT3A receptors. These observations suggest that the LC1-5-HT3A receptor interaction contributes to a mechanism that regulates receptor desensitization kinetics. Such dynamic regulation may play a role in reshaping the efficacy of 5-HT3 receptor-mediated synaptic transmission.

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