This heightened activity only occurred when less NKCC and less Quasimodo were present than normal.

In addition to the abnormal rhythmic behavior in constant light, the researchers also noticed another conspicuous behavior in some flies which were exposed to a long day-night cycle (16 hours light, eight hours dark): abnormally high activity in the morning. It was already known in the case of mammals-but not of flies-that the activity of NKCC and its counterpart plays an important role in the internal clock. 'What is interesting,' says Eick, 'is that the two cotransporters NKCC and KCC, as well as the kinases Wnk and Fray are-from an evolutionary point of view-very old proteins which occur not only in flies, but also in mammals. 'It is assumed that it depends for example on the time of day-and it might explain different behaviors in the fly by day and by night.' The activity of the cotransporter is regulated by two enzymes, the kinases 'Wnk' and 'Fray.' The researchers also took a close look at these two kinases. 'One and the same signal can act as a stimulator or an inhibitor,' explains lead author Katharina Eick. When there is a high chloride content, GABA has a stimulating effect when the content is low, it inhibits signal transmission through the cell. And this, in turn, is decisive for the functioning of the internal clock: the chloride content determines how a neuron reacts to the neurotransmitter GABA. The balance between these two cotransporters determines the chloride content in the cell. In this new study, published in the journal Current Biology, the researchers examined, for the first time, the counterpart of NKCC-the potassium chloride cotransporter KCC, which transports chloride ions out of the cell. Its function is to transport chloride ions into the cell.

Quasimodo interacts with a sodium-potassium-chloride cotransporter called NKCC. It is part of the cell membrane and helps to pass on light signals as external regulators and trigger an internal molecular regulatory cascade. The background is as follows: a protein known as Quasimodo is involved in the regulation of the internal clock of the fruit fly. The ion transport protein examined is part of a molecular signaling cascade in certain neurons in the brain.

A timepiece fruit