Neuroendocrine control of calcium mobilization in the fruit fly

Calcium (Ca²⁺) is an essential mineral that must be strictly regulated to support numerous physiological activities^1,2. Extracellular fluid Ca²⁺ is regulated in vertebrates through endocrine systems that manage the vast Ca²⁺ reservoir in the bones^3-6, but the Ca²⁺ regulatory mechanisms used by invertebrates, which lack bones, remain largely unclear. Here we identified a potent peptide hormone, Capa, which is responsible for regulating extracellular fluid Ca²⁺ levels in the fruit fly Drosophila melanogaster. Capa-deficient larvae exhibit low haemolymph Ca²⁺ levels, resulting in reduced locomotion and induced elongated pupae that mimic those of animals reared on a Ca²⁺-free diet. Capa secreted from specific neurosecretory cells acts on specialized Ca²⁺ storage compartments in the anterior Malpighian tubules, elevating haemolymph Ca²⁺. This endocrine mechanism governing Ca²⁺ regulation in terrestrial invertebrates resembles the parathyroid hormone system in vertebrates.