Cryptochrome and magnetosensitivity in Drosophila

许多动物利用地球磁场作为指南针和地图来帮助迁徙。然而，动物磁感受的确切生物学起源仍不清楚。有人提出，对于动物来说，要利用“地磁”信息，必须有一种最初检测地球磁场的东西（“受体”或“传感器”），并通过这种方式将这些信息传递给神经元中的关键分子（“反应者”）。在中枢神经系统（CNS）触发的变化导致动物对磁场做出反应。在被提出的主要磁传感器中，CRYPTOCHROME蛋白（CRY）。然而，在现实世界条件下，无论是CRY还是任何其他提出的磁感受器，都没有最终证明能直接在中枢神经系统的活动中产生磁诱导反应。在实验室中，我们使用细胞（中枢神经元的电活动）和整个生物体（运动行为）分析来证明果蝇（Drosophila melanogaster）对哭泣依赖的磁场效应具有实质性和可重复性。引人注目的是，我们已经证明，当只有一小部分CRY存在时，这种效应仍然存在。这严重破坏了既定的观点，即只有一个确定的生物物理反应，需要全长的哭声是必要的，足以使哭声成为磁传感器。相反，我们假设细胞有额外的方式来感知磁场。例如，我们有证据表明，黄素腺嘌呤二核苷酸（FAD），一种存在于所有细胞中的有机分子，与CRY结合，本身（作为一种自由分子）能接受磁场。因此，我们的假设之一是，上述小CRY片段介导的磁响应可能反映了游离FAD对磁传感的放大。这意味着，自由的FAD以某种方式与小的CRY片段“耦合”起来。或者，“传感器”可能是一种能够与CRY片段结合的不同蛋白质。我们认为，CRY发挥作用的关键在于，它能够将“传感器”带到细胞“应答者”附近，这需要小CRY片段携带的氨基酸基元。我们将通过遗传学和生物化学来测试这些假设，然后进行神经生物学和行为研究。一个积极的结果将通过建立一种思考动物细胞磁感受的新方法，对该领域产生重大影响。

Many animals use the Earth's magnetic field as a compass and map to aid migration. However, the precise biological origin of animal magnetoreception remains unclear. It is proposed that for an animal to make use of 'geomagnetic' information, there must be something that initially detects the Earth's magnetic field (a 'receptor' or 'sensor') and means by which this information is communicated to critical molecules ('responders') in neurons. Changes triggered in the central nervous system (CNS) result in the animal responding to the magnetic field.Among the proposed primary magnetosensors is the protein CRYPTOCHROME (CRY). However, neither CRY, nor any other proposed magnetoreceptor, has been conclusively shown to directly produce a magnetically-induced response in the activity of the CNS under real-world conditions. In the laboratory, we have used cellular (electrical activity of central neurons) and whole organism (locomotor behaviour) assays to demonstrate a substantial and reproducible CRY-dependent magnetic field effect in the fruit fly, Drosophila melanogaster. Strikingly, we have shown that this effect persists when just a small fragment of CRY is present. This seriously undermines the established view that only a determined biophysical reaction that requires full-length CRY is necessary and sufficient to make CRY a magnetosensor. Instead, we hypothesize that cells have additional modalities at their disposal to sense magnetic fields. For instance, we have evidence that Flavin Adenine Dinucleotide (FAD), an organic molecule present in all cells, and which CRY binds to, is per se (as a free molecule) receptive to magnetic fields. Therefore, one of our hypotheses is that the magnetic response mediated by the aforementioned small CRY fragment, might reflect an amplification of magnetic sensing by free FAD. The implication is that somehow, free FAD becomes 'coupled' to the small CRY fragment. Alternatively, the 'sensor' could be a different protein able to bind to the CRY fragment. What we think is key to CRY's role, is its ability to bring the 'sensor' near the cellular 'responders', which requires amino acid motifs carried by the small CRY fragment. We will test these hypotheses using genetics and biochemistry to set the scene and then by conducting neurobiological and behavioural investigations. A positive outcome will have a significant impact to the field by establishing a new way of thinking about magnetoreception in animal cells.