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Modulation of 5‐HT 3 receptor desensitization by the light chain of microtubule‐associated protein 1B expressed in HEK 293 cells
Author(s) -
Sun Hui,
Hu XiangQun,
Emerit Michel B.,
Schoenebeck Jeffrey C.,
Kimmel Cassin E.,
Peoples Robert W.,
Miko Angela,
Zhang Li
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.136440
Subject(s) - receptor , hek 293 cells , nocodazole , microbiology and biotechnology , agonist , 5 ht receptor , chemistry , ion channel , ligand gated ion channel , desensitization (medicine) , biophysics , biology , serotonin , cytoskeleton , biochemistry , cell
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‐HT 3 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‐HT 3 receptor‐mediated synaptic transmission.