Recovery from tachyphylaxis of TRPV1 coincides with recycling to the surface membrane

Proceedings of the National Academy of Sciences of the United States of America
Quan TianJing Yao

Abstract

The transient receptor potential vanilloid-1 (TRPV1) ion channel is essential for sensation of thermal and chemical pain. TRPV1 activation is accompanied by Ca2+-dependent desensitization; acute desensitization reflects rapid reduction in channel activity during stimulation, whereas tachyphylaxis denotes the diminution in TRPV1 responses to repetitive stimulation. Acute desensitization has been attributed to conformational changes of the TRPV1 channel; however, the mechanisms underlying the establishment of tachyphylaxis remain to be defined. Here, we report that the degree of whole-cell TRPV1 tachyphylaxis is regulated by the strength of inducing stimulation. Using light-sheet microscopy and pH-sensitive sensor pHluorin to follow TRPV1 endocytosis and exocytosis trafficking, we provide real-time information that tachyphylaxis of different degrees concurs with TRPV1 recycling to the plasma membrane in a proportional manner. This process controls TRPV1 surface expression level thereby the whole-cell nociceptive response. We further show that activity-gated TRPV1 trafficking associates with intracellular Ca2+ signals of distinct kinetics, and recruits recycling routes mediated by synaptotagmin 1 and 7, respectively. These results...Continue Reading

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Citations

Jul 3, 2019·Channels·Francina Agosti, Christophe Altier
Feb 8, 2020·International Journal of Molecular Sciences·Péter SánthaGábor Jancsó
Jun 18, 2020·Scientific Reports·Masayoshi KawaseMakoto Kanzaki
Jan 5, 2021·Frontiers in Physiology·Michael J M FischerArpad Szallasi
Oct 17, 2020·The Journal of Biological Chemistry·Yuanyuan WangJing Yao
Feb 27, 2021·Frontiers in Cell and Developmental Biology·Juan HuJing Yao
Jan 18, 2021·The Journal of Biological Chemistry·Yuanyuan WangJing Yao
Aug 2, 2020·Chemico-biological Interactions·Manal Ahmad Abbas

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