Unexpected divergence in magnetoreceptor MagR from robin and pigeon linked to two sequence variations

Birds exhibit extraordinary mobility and remarkable navigational skills,obtaining guidance cues from the Earth’s magnetic field for orientation and long-distance movement.Bird species also show tremendous diversity in navigation strategies,with considerable differences even within the same taxa and among individuals from the same population.The highly conserved iron and iron-sulfur cluster binding magnetoreceptor(MagR)protein is suggested to enable animals,including birds,to detect the geomagnetic field and navigate accordingly.Notably,MagR is also implicated in other functions,such as electron transfer and biogenesis of iron-sulfur clusters,raising the question of whether variability exists in its biochemical and biophysical features among species,particularly birds.In the current study,we conducted a comparative analysis of MagR from two different bird species,including the migratory European robin(Erithacus rubecula)and the homing pigeon(Columba livia).Sequence alignment revealed an extremely high degree of similarity between the MagRs of these species,with only three sequence variations.Nevertheless,two of these variations underpinned significant differences in metal binding capacity,oligomeric state,and magnetic properties.These findings offer compelling evidence for the marked differences in MagR between the two avian species,potentially explaining how a highly conserved protein can mediate such diverse functions.

Mitochondrial targeting sequence of magnetoreceptor MagR:More than just targeting

Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein IscA1(or MagR)is found within the mitochondria of most eukaryotes.Magnetoreceptor(MagR)is a highly conserved A-type iron and iron-sulfur cluster-binding protein,characterized by two distinct types of iron-sulfur clusters,[2Fe-2S]and[3Fe-4S],each conferring unique magnetic properties.MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome(Cry)and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation.Although the N-terminal sequences of MagR vary among species,their specific function remains unknown.In the present study,we found that the N-terminal sequences of pigeon MagR,previously thought to serve as a mitochondrial targeting signal(MTS),were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound.Moreover,the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex.Thus,the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting.These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.

On the evolutionary trail of MagRs

Magnetic sense,or termed magnetoreception,has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation.MagRs,highly conserved A-type iron-sulfur proteins,are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis.However,the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear.In this study,MagR sequences from 131 species,ranging from bacteria to humans,were selected for analysis,with 23 representative sequences covering species from prokaryotes to Mollusca,Arthropoda,Osteichthyes,Reptilia,Aves,and mammals chosen for protein expression and purification.Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution.Three types of MagRs were identified,each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability,indicating continuous expansion of the functional roles of MagRs during speciation and evolution.This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs.

Magnetogenetics: remote non-invasive magnetic activation of neuronal activity with a magnetoreceptor

Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a mag- netoreceptor with remote magnetic stimulation. The noninvasive activation of neurons was achieved by neuronal expression of an exogenous magnetoreceptor, an iron-sulfur cluster assembly protein 1 （Iscal）. In HEK-293 cells and cultured hippocampal neurons expressing this magnetoreceptor, application of an external magnetic field resulted in membrane depolarization and calcium influx in a reproducible and reversible manner, as indicated by the ultrasensitive fluorescent calcium indicator GCaMP6s.Moreover, the magnetogenetic control of neuronal activity might be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for the external magnetic field applied. The activation of this magnetoreceptor can depolarize neurons and elicit trains of action potentials, which can be triggered repetitively with a remote magnetic field in whole-cell patch-clamp recording. In transgenic Caenorhabditis elegans expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4- specific neurons, application of the external magnetic field triggered muscle contraction and withdrawal behavior of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons, respectively. The advantages of magnetogenetics over optogenetics are its exclusive non-invasive, deep penetration, long-term continuous dosing, unlimited accessibility, spatial uniformity and relative safety. Like optogenetics that has gone through decade-long improvements, magnetogenetics, with continuous modification and maturation, will reshape the current landscape of neuromodulation toolboxes and will have a broad range of applications to basic and translational neuroscience as well as other biological sciences. We envision a new age of magnetogenetics is coming.

Towards magnetism in pigeon MagR: Iron- and iron-sulfur binding work indispensably and synergistically

The ability to navigate long distances is essential for many animals to locate shelter,food,and breeding grounds.Magnetic sense has evolved in various migratory and homing species to orient them based on the geomagnetic field.A highly conserved ironsulfur cluster assembly protein IscA is proposed as an animal magnetoreceptor(MagR).Iron-sulfur cluster binding is also suggested to play an essential role in MagR magnetism and is thus critical in animal magnetoreception.In the current study,we provide evidence for distinct iron binding and iron-sulfur cluster binding in MagR in pigeons,an avian species that relies on the geomagnetic field for navigation and homing.Pigeon MagR showed significantly higher total iron content from both iron-and ironsulfur binding.Y65 in pigeon MagR was shown to directly mediate mononuclear iron binding,and its mutation abolished iron-binding capacity of the protein.Surprisingly,both iron binding and iron-sulfur binding demonstrated synergistic effects,and thus appear to be integral and indispensable to pigeon MagR magnetism.These results not only extend our current understanding of the origin and complexity of MagR magnetism,but also imply a possible molecular explanation for the huge diversity in animal magnetoreception.

生物磁铁矿的磁各向异性与磁接收器

磁铁矿是分布广泛且非常重要的亚铁磁材料,也广泛分布在生物体中.生物体中的磁铁矿具有完美的晶体结构,大多为超顺磁颗粒或单畴颗粒,且大多呈链状分布,具有明显的磁各向异性.生物体中存在"磁接收器",生物磁铁矿是"磁接收器"的生物物理基础.本文中,从超顺磁磁铁矿颗粒和单畴磁铁矿颗粒的物理特性出发,主要是从它们的磁各向异性特性的基础上描述了生物磁铁矿和"磁接收器"的工作机制,即在某些条件下,在外界地磁场强度量级的磁场作用下,超顺磁颗粒或单畴颗粒可以诱导产生足够强的磁场,使邻近的晶体可以相互吸引或排斥,这些粒子间的相互作用可以改变晶体颗粒束所在的外围机体形状,而神经系统可以探测到单独的粒子束或一列粒子束的扩张或收缩,因此生物体就可以探测到磁场的方向以及强度等磁场参量.

眼非视觉功能在生物感磁过程中的作用

眼的非视觉功能包括生物昼夜节律的调节以及生物感磁。生物感磁是指各种生物包括人类可通过地磁场获取方向位置信息。具有视网膜结构的生物可能是以视网膜隐花色素蛋白作为磁受体,完成生物感磁过程。生物感磁的假说分别是基于化学反应和自由基对的磁感应假说以及光磁耦合的生物指南针假说。这2个假说都认为视网膜上的分子可能是生物感磁的受体蛋白,眼可能是生物感磁的器官。但基于化学反应和自由基对的磁感应假说认为是通过自由基电子自旋方式的改变,影响了视网膜隐花色素蛋白的分子结构,引起下游化学反应产生不同的化学产物,从而感受到磁场的变化;光磁耦合的生物指南针假说指出隐花色素蛋白作为光受体,与另一种磁受体蛋白经过多聚反应形成棒状小体,光信号和磁信号的耦合影响了棒状的复合体指向的变化。这些视网膜上的改变再通过某种途径传输至大脑,从而产生方向感。研究生物感磁有助于从新的角度诊断和治疗眼脑疾病,并且带来磁敏材料领域的革新。本文就眼非视觉功能、生物感磁过程的机制假说和眼非视觉功能在生物感磁过程中可能的作用机制进行综述。

磁铁矿磁感受器神经信号转换过程

生物中磁感受器机制是理解生物磁导航的生物物理机制,磁信息转换成神经信息的过程是这一机制的核心,但是仍然处于假设阶段.本文中首先综述了电磁感应机制、基于磁蛋白的磁感知机制和磁铁矿纳米颗粒的磁感知机制中神经信号转变过程,最后提出了从理论上认识磁铁矿磁感受器神经信号转换过程的可能途径.

生物磁铁矿与磁接收器

很多生物的行为受到地磁场的影响,并利用地磁场作为长距离迁移和飞行的信息.研究者认为,这些生物体内存在磁接收器,是磁接收器接收到地磁信息并传递给神经组织.由于生物磁铁矿在生物体中的广泛存在,以生物磁铁矿为基础的磁接收器机制被提出.本文中主要综述了生物磁铁矿的物理特性、与神经组织的关系、以生物磁铁矿为基础的磁接收器模型以及某些实验验证结果.

家鸽头部的磁性物质

磁铁矿可以在很多生物组织中被发现,国外研究者同样在家鸽上喙皮肤组织中发现了规则分布的超顺磁磁铁矿颗粒。他们应用透射电子显微镜确认了这些小磁铁矿晶体为尺寸在1—5 nm的聚集体,集中存在于皮下组织中。这些超顺磁粒子聚集体又形成直径为1—3μm的粒子束,分布在大细胞之间的长形结构中,并且与神经组织紧密相连。应用光学显微镜和电子显微镜,国外研究者也对家鸽上喙传入三叉神经末梢的次细胞组织进行了研究。这些神经末梢组织直径大约5μm,内部包含着聚集成束的超顺磁磁铁矿颗粒。大约10到15个粒子束存在于一个神经末梢中,沿着细胞膜排列。每一个超顺磁粒子束包埋在一个纤维杯中,口朝向细胞表面,通过纤维组织,这些粒子束粘附在细胞表面上。除了超顺磁颗粒,非晶态铁磷酸盐也被发现,它们沿着神经末梢的纤维中心分布。解剖特征表明,这些神经末端可以探测很小的地磁场强度的变化,考虑到以超顺磁磁铁矿颗粒为基础的"磁接收器"理论,他们还给出了几个"磁接收器"的模型。