Cryptochrome and magnetosensitivity in Drosophila

果蝇的隐花色素和磁敏感性

• 批准号: BB/V005987/1
• 负责人: Richard Baines
• 金额: $ 52.09万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV005987%2F1
• 关键词: Cryptochrome; magnetosensitivity; Drosophila

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.

许多动物利用地球的磁场作为指南针和地图来帮助迁移。然而，动物磁感受的确切生物起源仍然不清楚。有人提出，动物要利用“地磁”信息，必须有一些东西最初检测地球的磁场（“受体”或“传感器”），并通过这些信息传达给神经元中的关键分子（“响应者”）。中枢神经系统（CNS）的变化导致动物对磁场产生反应，其中一种主要的磁传感器是蛋白质CRY。然而，无论是CRY，还是任何其他提出的磁感受器，都没有最终显示出在真实世界条件下直接产生CNS活动中的磁诱导反应。在实验室中，我们已经使用细胞（中央神经元的电活动）和整个有机体（运动行为）的测定，以证明一个实质性的和可重复的磁场依赖的果蝇，果蝇的磁场效应。令人惊讶的是，我们已经证明，当只存在一小部分CRY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CRY是必要的，并足以使CRY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，CRY与之结合，本身（作为一种自由分子）接受磁场。因此，我们的假设之一是，由上述小CRY片段介导的磁响应可能反映了游离FAD对磁感应的放大。这意味着，游离FAD以某种方式与小的CRY片段“耦合”。或者，“传感器”可以是能够结合CRY片段的不同蛋白质。我们认为CRY作用的关键是它能够将“传感器”带到细胞“反应器”附近，这需要小CRY片段携带的氨基酸基序。我们将使用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调查。一个积极的结果将通过建立一种新的思考动物细胞磁感受的方式对该领域产生重大影响。

项目成果

Essential elements of radical pair magnetosensitivity in Drosophila.

• DOI: 10.1038/s41586-023-05735-z
• 发表时间: 2023-03
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Bradlaugh, Adam A.;Fedele, Giorgio;Munro, Anna L.;Hansen, Celia Napier;Hares, John M.;Patel, Sanjai;Kyriacou, Charalambos P.;Jones, Alex R.;Rosato, Ezio;Baines, Richard A.
• 通讯作者: Baines, Richard A.

Essential elements of radical pair magnetosensitivity in Drosophila

果蝇自由基对磁敏感性的基本要素

• DOI: 10.1101/2021.10.29.466426
• 发表时间: 2021
• 作者: Bradlaugh A