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This Article Full Text Full Text (PDF) All Versions of this Article: 586/3/751    most recent jphysiol.2007.136440v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sun, H. Articles by Zhang, L. Search for Related Content PubMed PubMed Citation Articles by Sun, H. Articles by Zhang, L. Related Collections Neuroscience

¹ Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Bethesda, MD 20892, USA
² INSERM U677, Neuropsychopharmacologie Moléculaire, Cellulaire et Fonctionelle, C.H.U. Pitié-Salpêtrière, 91 Bd de l'Hôpital, 75634 Paris Cedex 13, France
³ Department of Biomedical Sciences, College of Health Sciences, Marquette University, Milwaukee, WI 53201-1881, USA

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-HT_3A receptor, a predominant serotonin-gated ion channel in the brain. LC1 and 5-HT_3A receptors were colocalized in central neurons and in HEK 293 cells expressing 5-HT_3A receptors. LC1 reduced the steady-state density of 5-HT_3A 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-HT_3A 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-HT_3A receptors. These observations suggest that the LC1–5-HT_3A 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.

(Received 6 July 2007; accepted after revision 21 November 2007; first published online 6 December 2007)
Corresponding author L. Zhang: Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, TS24, Bethesda, MD 20892, USA. Email: lzhang{at}mail.nih.gov