Watanabe, A., Koyama, T., Kubrak, O., Texada, M.J., Furumitsu, M., Iwakoshi-Ukena, E., Maxson, R., Yoshii, T., Kondo, S., Yamanaka, N., Ukena, K., Rewitz, K., Niwa, R., Okamoto, N. (2026). Ion transport peptide regulates larval body water balance via a receptor guanylyl cyclase in Drosophila.  iScience 29(6): 116252.

FBrf0265693

Research paper

Maintaining internal water balance, including ionic and osmotic homeostasis, is critical for animal development and survival. Water balance is controlled by multiple hormones, but the underlying endocrine mechanisms remain largely unknown. Here, we show that the short amidated isoform of ion transport peptide (saITP), secreted from brain neurosecretory cells, regulates larval body water balance via the receptor guanylyl cyclase (rGC) Gyc76C in the hindgut of the fruit fly Drosophila melanogaster, forming a brain-hindgut neuroendocrine axis. Both ITP and Gyc76C are evolutionarily conserved among ecdysozoans and are essential for larval survival. Synthetic saITP markedly increased intracellular cGMP in a Gyc76C-dependent manner in cultured Drosophila S2 cells, heterologous human cells, and ex vivo-cultured larval hindguts. Hindgut-specific Gyc76C knockdown eliminated the saITP-induced water reabsorption effect. Our study provides new insight into the brain-gut axis control of osmoregulation in ecdysozoans and supports a broader role for rGCs in peptide-hormone signaling.

PMC13267572 (PMC) (EuropePMC)