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

• DOI: 10.1113/jphysiol.2007.136440
• Publication Date: 2007-12-07T01:39:50Z
• Authors: Hui Sun; Xiang‐Qun Hu; Michel B. Emerit; Jeffrey C. Schoen...; Cassin E. Kimmel; Robert W. Peoples; Angela Miko; Li Zhang
• Keywords: Neurons; 0301 basic medicine; Nocodazole; Cell Membrane; Nerve Tissue Proteins; Oligonucleotides, Antisense; Kidney; Hippocampus; Microtubules; Tubulin Modulators; Cell Line; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Animals; Humans; Female; Receptors, Serotonin, 5-HT3; Apoptosis Regulatory Proteins; Microtubule-Associated Proteins; Cells, Cultured; Adaptor Proteins, Signal Transducing

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. LC1 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 GABAA 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.