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Reposted by Candie Paulsen Lab

Yale Neuroscience @yaleneuro.bsky.social · 13/11/2025

In a new @natcomms.nature.com study, @yale.edu's @paulsenlab.bsky.social uncovers how the protein calmodulin regulates pain signaling! ⚡ This breakthrough could lead to better pain management strategies 💊 Read More 👇 news.yale.edu/2025/09/30/u...

news.yale.edu

Unraveling a painful mystery: Protein plays key role in modulating pain response

A new Yale study has uncovered the hidden mechanical move that may regulate pain signaling in the human body — and why it sometimes goes awry.

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Candie Paulsen Lab @paulsenlab.bsky.social · 02/10/2025

🧠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

rdcu.be

Calmodulin binding is required for calcium mediated TRPA1 desensitization

Nature Communications - For pain signaling to be useful, sensory receptors must rapidly detect noxious stimuli and efficiently turn off once the threat has passed. Here, the authors uncover a...

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Candie Paulsen Lab @paulsenlab.bsky.social · 24/02/2025

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!

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Reposted by Candie Paulsen Lab

Gabriela K Popescu @popstarlab.bsky.social · 18/02/2025

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

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Candie Paulsen Lab @paulsenlab.bsky.social · 13/12/2024

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!

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Candie Paulsen Lab @paulsenlab.bsky.social · 13/12/2024

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?

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Candie Paulsen Lab @paulsenlab.bsky.social · 13/12/2024

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.

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Candie Paulsen Lab @paulsenlab.bsky.social · 13/12/2024

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.

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Candie Paulsen Lab @paulsenlab.bsky.social · 13/12/2024

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.

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Candie Paulsen Lab @paulsenlab.bsky.social · 13/12/2024

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.

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Candie Paulsen Lab @paulsenlab.bsky.social · 13/12/2024

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...

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