Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on “toxin sponge” proteins
Abstract
Many poisonous organisms carry small-molecule toxins that alter voltage-gated sodium channel (NaV) function. Among these, batrachotoxin (BTX) from Pitohui poison birds and Phyllobates poison frogs stands out because of its lethality and unusual effects on NaV function. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a NaV DIVS6 pore-forming helix N-to-T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent from Pitohui and poison frog NaVs, incurs a strong cost compromising channel function, and fails to produce BTX-resistant channels in poison frog NaVs. We also show that captivity-raised poison frogs are resistant to two NaV-directed toxins, BTX and saxitoxin (STX), even though they bear NaVs sensitive to both. Moreover, we demonstrate that the amphibian STX “toxin sponge” protein saxiphilin is able to protect and rescue NaVs from block by STX. Taken together, our data contradict the hypothesis that BTX autoresistance is rooted in the DIVS6 N→T mutation, challenge the idea that ion channel mutations are a primary driver of toxin resistance, and suggest the possibility that toxin sequestration mechanisms may be key for protecting poisonous species from the action of small-molecule toxins.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 05, 2021
- Source ID
- 10.1085/jgp.202112872
Entities
People
- Catherine E. Garrison
- Claire M. Colleran
- Daniel L Minor
- Fayal Abderemane-ali
- J. Du Bois
- John P. Dumbacher
- Lauren A. O'Connell
- Megan E Kobiela
- Nathan D. Rossen
- Robert A Craig
- Zhou Chen
Organizations
- American Heart Association
- American Ornithological Society
- California Academy of Sciences
- Lawrence Berkeley National Laboratory
- National Geographic Society
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- National Institute on Deafness and Other Communication Disorders
- National Science Foundation
- San Francisco State University
- Stanford University
- United States Department of Defense
- University of California
- University of California, San Francisco
- University of Nebraska–Lincoln