Biology: Hodor holds the door to insect food intake

A nutrient-sensing protein called Hodor, found in the intestines of fruit flies, that has a role in regulating food intake and developmental growth, is reported in Nature. Blocking this insect-specific protein could be used as a way to control populations of disease-carrying insects, such as mosquitoes.

Cells and organisms need to sense nutrients to maintain internal stability (homeostasis) and adapt to changing conditions in their surrounding environment. Micronutrients, such as metal ions, are known to have important roles in growth and development, but our understanding of how metals are sensed is limited. To learn more, Irene Miguel-Aliaga and colleagues study the intestines of fruit flies (Drosophila melanogaster), as the gastrointestinal tract is known to have a role in energy homeostasis. They performed a genetic screen of over 100 candidate proteins thought to be involved in nutrient sensing. This screen uncovered a receptor that seems to regulate the development of larvae, particularly in nutrient-poor conditions. Inhibiting the expression of this protein resulted in developmental delay, as referenced in the name ‘Hodor’ (an abbreviation for ‘hold on, don’t rush’).

Hodor is a zinc-sensing protein that uses the metal to transport chloride within and out of cells, facilitating pathways that regulate nutrient-sensing and growth. Increasing the levels of zinc in the flies’ diet led to increased feeding, which was reversed when Hodor was blocked. The authors suggest that the receptor helps to direct the animals to nutrient-rich food sources (metals such as zinc are produced by yeasts, which are found on fruit and other foods). Finally, they demonstrate that deleting the gene in mosquitoes is fatal, suggesting that such disease vectors could be targeted and controlled by using ingestible drugs.