Back

Calpain cleaves the carboxyl terminus of TRPV1 and modulates receptor tachyphylaxis

Jiang, J.; Wang, X.; Yang, J.; Gao, S.; Xu, J.; Liu, J.; Wang, Y.; Liang, P.; Zhang, Y.

2025-05-02 neuroscience Community evaluation
10.1101/2025.04.28.651151 bioRxiv
Show abstract

Transient receptor potential vanilloid-1 (TRPV1) plays a critical role in noxious heat sensation and pain hypersensitivity development in chronic pain. Sustained or repeated exposure to capsaicin, a classic TRPV1 agonist, induces TRPV1 desensitization. This partially accounts for the analgesic effect of capsaicin. However, the regulatory mechanisms of TRPV1 desensitization remain poorly understood. In this study, we found that capsaicin acts on TRPV1 to induce the activation of calpain, a Ca2+-sensitive cysteine protease, in a manner unrelated to cellular injury. Calpain cleaves rTRPV1 at the carboxyl terminus of G819/S820. Lack of the distal carboxyl terminus leads to reduced TRPV1 localization on the plasma membrane, potentially due to increased receptor internalization and impaired subunit assembly. This finding was corroborated by whole-cell patch clamp recordings. Additionally, the {Delta}820-838 mutant of rTRPV1 shows resistance to tachyphylaxis as induced by repetitive capsaicin stimulation. This study reveals a pivotal role for calpain in TRPV1 desensitization where its activation constrains TRPV1 channel function while simultaneously increasing its resistance to tachyphylaxis, thereby acting to maintain TRPV1 activity within an appropriate range.

Matching journals

The top 13 journals account for 50% of the predicted probability mass.

1
eLife
● 5828 papers in training set
Top 8%
11.9%
Similar papers in this journal
2
Scientific Reports
○ 3612 papers in training set
Top 10%
6.7%
Similar papers in this journal
3
Journal of Biological Chemistry
○ 690 papers in training set
Top 2%
4.3%
Similar papers in this journal
4
iScience
○ 1154 papers in training set
Top 4%
4.0%
Similar papers in this journal
5
International Journal of Molecular Sciences
○ 494 papers in training set
Top 3%
3.4%
Similar papers in this journal
6
Cell Death & Disease
147 papers in training set
Top 0.8%
3.2%
7
Journal of General Physiology
● 60 papers in training set
Top 0.2%
3.2%
8
Pain
○ 78 papers in training set
Top 0.5%
2.6%
9
Frontiers in Pharmacology
○ 111 papers in training set
Top 0.8%
2.6%
10
PLOS ONE
● 5266 papers in training set
Top 40%
2.4%
11
Communications Biology
○ 993 papers in training set
Top 9%
2.4%
12
The FEBS Journal
○ 93 papers in training set
Top 0.4%
2.4%
13
Cell Calcium
○ 18 papers in training set
Top 0.1%
2.1%
50% of probability mass above
14
Cell Death Discovery
○ 58 papers in training set
Top 0.4%
2.1%
15
Cells
○ 249 papers in training set
Top 2%
2.1%
16
Nature Communications
○ 5641 papers in training set
Top 43%
1.9%
17
Cell Reports
○ 1498 papers in training set
Top 18%
1.9%
18
Molecular and Cellular Neuroscience
○ 20 papers in training set
Top 0.1%
1.9%
19
British Journal of Pharmacology
○ 40 papers in training set
Top 0.3%
1.9%
20
The FASEB Journal
○ 194 papers in training set
Top 3%
1.5%
21
Theranostics
● 37 papers in training set
Top 0.5%
1.5%
22
ACS Chemical Neuroscience
● 67 papers in training set
Top 0.9%
1.3%
23
Biochemical and Biophysical Research Communications
○ 84 papers in training set
Top 1%
1.3%
24
Advanced Science
○ 286 papers in training set
Top 7%
1.1%
25
Signal Transduction and Targeted Therapy
○ 30 papers in training set
Top 0.4%
1.1%
26
The Journal of Pain
○ 30 papers in training set
Top 0.4%
1.1%
27
The Journal of Neuroscience
● 1025 papers in training set
Top 9%
1.1%
28
Neuroscience Letters
○ 32 papers in training set
Top 0.4%
1.1%
29
Brain Research
○ 38 papers in training set
Top 0.6%
1.0%
30
Science Advances
● 1243 papers in training set
Top 28%
1.0%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.