A specific folate activates serotonergic neurons to control C. elegans behavior

Ria S. Peesapati, Brianna L. Austin-Byler, Fathima Zahra Nawaz, Jonathan B. Stevenson, Stanelle A. Mais, Rabia N. Kaya, Michael G. Hassan, Nabraj Khanal, Alexandra C. Wells, Deena Ghiai, Anish K. Garikapati, Jacob Selhub and Edward T. Kipreos ()
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Ria S. Peesapati: The University of Georgia
Brianna L. Austin-Byler: The University of Georgia
Fathima Zahra Nawaz: The University of Georgia
Jonathan B. Stevenson: The University of Georgia
Stanelle A. Mais: The University of Georgia
Rabia N. Kaya: The University of Georgia
Michael G. Hassan: The University of Georgia
Nabraj Khanal: The University of Georgia
Alexandra C. Wells: The University of Georgia
Deena Ghiai: The University of Georgia
Anish K. Garikapati: The University of Georgia
Jacob Selhub: Tufts University
Edward T. Kipreos: The University of Georgia

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Folates are B-group vitamins that function in one-carbon metabolism. Here we show that a specific folate can activate serotonergic neurons in C. elegans to modulate behavior through a pathway that requires the folate receptor FOLR-1 and the GON-2 calcium channel. FOLR-1 and GON-2 physically interact in a heterologous system, and both are expressed in the HSN and NSM serotonergic neurons. Both the folate 10-formyl-THF and a non-metabolic pteroate induce increases in the number of Ca2+ transients in the HSN neurons and egg laying in an FOLR-1- and GON-2-dependent manner. FOLR-1 and GON-2 are required for the activation of the NSM neurons in response to 10-formyl-THF, and for full NSM-mediated stoppage of movement when starved animals encounter bacteria. Our results demonstrate that FOLR-1 acts independently of one-carbon metabolism and suggest that 10-formyl-THF acts as a dietary signal that activates serotonergic neurons to impact behavior through a pathway that involves calcium entry.

Date: 2024
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DOI: 10.1038/s41467-024-52738-z

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