🧠Pain sensors need to switch on fast—and off just as quickly.

In our new tour de force Nat Comms paper - led by the first Paulsen lab grad student - we show that calmodulin plays a key role in shutting down the TRPA1 pain receptor - a finding that could guide new pain therapies.

📰 rdcu.be/eJcMK

We had a great time at BPS 2025– learned a lot and made great connections. Congrats to Paulsen Lab grad student Isabel Romov for winning a Student Research Achievement Award! We celebrated at Disneyland. ‘Til next year!

Suffragists famously wore white as a symbol of purity, morality, and the quest for equality.

My sartorial decision to wear (mostly) white at #BPS2025 was meant as a reminder of the ongoing fight for gender equality and the importance of continued advocacy for women’s rights.
#womeninscience

6. Our work also raises interesting questions about whether endogenous TRPA1 modifications can perturb the TRPA1:calmodulin interaction to influence channel regulation. So many exciting questions to ask!

5. Together, our work suggests that calmodulin pre-associates with TRPA1 in cells to facilitate proper calcium regulation. Perhaps calmodulin is a TRPA1 auxiliary subunit?

4. Using a combination of biochemical, biophysical, and structural approaches, we characterized the TRPA1 DCTCaMBE:calmodulin interaction and found that it is driven exclusively by the calmodulin C-lobe with tightest binding observed at basal calcium concentration.

3. This effect could be partially rescued by increasing the extracellular calcium concentration, suggesting that calmodulin binding to the DCTCaMBE is part of a multi-step long-range allosteric mechanism to control TRPA1 inactivation.

2. We identified a highly conserved calmodulin binding site in the TRPA1 distal, structurally unresolved, cytoplasmic C-terminus (the DCTCaMBE). Genetic or biochemical ablation of calmodulin binding to this site slowed TRPA1 calcium inactivation 10-to-20 fold.

1. Calcium regulation is the primary TRPA1 regulatory mechanism that keeps its activity in check to sustain acute pain signaling and prevent aberrant signaling. This regulation is biphasic with initial channel potentiation followed by inactivation/desensitization. Mechanism has been unclear.

We are delighted to share the next story from the Paulsen lab! In a team effort led by Candie's first Yale grad student, Justin Sanders, we've uncovered a critical role for calmodulin in the TRPA1 pain receptor's calcium regulation. Check it out here: www.biorxiv.org/content/10.1...