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 i...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.展开更多
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 I...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.展开更多
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 distribut...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.展开更多
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 geomagnet...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.展开更多
The morphology is the consequence of evolution and adaptation.Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5μm long and 0.5μm wide.Many shape-related genes have been identified and used ...The morphology is the consequence of evolution and adaptation.Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5μm long and 0.5μm wide.Many shape-related genes have been identified and used in morphology engineering of this bacteria.However,little is known about if specific metabolism and metal irons could modulate bacteria morphology.Here in this study,we discovered filamentous shape change of E.coli cells overexpressing pigeon MagR,a putative magnetoreceptor and extremely conserved iron-sulfur protein.Comparative transcriptomic analysis strongly suggested that the iron metabolism change and iron accumulation due to the overproduction of MagR was the key to the morphological change.This model was further validated,and filamentous morphological change was also achieved by supplement E.coli cells with iron in culture medium or by increase the iron uptake genes such as entB and fepA.Our study extended our understanding of morphology regulation of bacteria,and may also serves as a prototype of morphology engineering by modulating the iron metabolism.展开更多
Magnetoreception is essential for magnetic orientation in animal migration. The molecular basis for magnetoreception has re- cently been elucidated in fruitfly as complexes between the magnetic receptor magnetorecept...Magnetoreception is essential for magnetic orientation in animal migration. The molecular basis for magnetoreception has re- cently been elucidated in fruitfly as complexes between the magnetic receptor magnetoreceptor （MagR） and its ligand crypto- chrome （Cry）. MagR and Cry are present in the animal kingdom. However, it is unknown whether they perform a conserved role in diverse animals. Here we report the identification and expression of zebrafish MagR and Cry homologs towards under- standing their roles in lower vertebrates. A single rnagr gene and 7 cry genes are present in the zebrafish genome. Zebrafish has four cryl genes （crylaa, crylab, crylba and cry]bb） homologous to human CRY1 and a single ortholog of human CRY2 as well as 2 cry-like genes （cry4 and cryS）. By RT-PCR, magr exhibited a high level of ubiquitous RNA expression in embryos and adult organs, whereas cry genes displayed differential embryonic and adult expression. Importantly, magr depletion did not produce apparent abnormalities in organogenesis. Taken together, magr and cry2 exist as a single copy gene, whereas cryl exists as multiple gene duplicates in zebrafish. Our result suggests that magr may play a dispensable role in organogenesis and predicts a possibility to generate rnagr mutants for analyzing its role in zebrafish.展开更多
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 im...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.展开更多
Magnetoreception is a hallmark ability of animals for orientation and migration via sensing and utilizing geomagnetic fields.Magnetoreceptor(MagR) and cryptochromes(Cry) have recently been identified as the basis for ...Magnetoreception is a hallmark ability of animals for orientation and migration via sensing and utilizing geomagnetic fields.Magnetoreceptor(MagR) and cryptochromes(Cry) have recently been identified as the basis for magnetoreception in Drosophila.However,it has remained unknown whether MagR and Cry have conserved roles in diverse animals.Here we report the identification and expression of magr and cry genes in the fish medaka(Oryzias latipes).Cloning and sequencing identified a single magr gene,four cry genes and one cry-like gene in medaka.By sequence alignment,chromosomal synteny and gene structure analysis,medaka cry2 and magr were found to be the orthologs of human Cry2 and Magr,with cry1 aa and crylab being coorthologs of human Cry1.Therefore,magr and cry2 have remained as single copy genes,whereas cry1 has undergone two rounds of gene duplication in medaka.Interestingly,magr and cry genes were detected in various stages throughout embryogenesis and displayed ubiquitous expression in adult organs rather than specific or preferential expression in neural organs such as brain and eye.Importantly,magr knockdown by morpholino did not produce visible abnormality in developing embryos,pointing to the possibility of producing viable magr knockouts in medaka as a vertebrate model for magnet biology.展开更多
基金supported by the National Natural Science Foundation of China(31640001 and T2350005 to C.X.,U21A20148 to X.Z.and C.X.)Ministry of Science and Technology of China(2021ZD0140300 to C.X.)Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.,E36CWGBR24B and E36CZG14132 to T.C.)。
文摘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.
基金supported by the National Natural Science Foundation of China(31640001 and T2350005 to C.X.,U21A20148 to X.Z.and C.X.)Ministry of Science and Technology of China(2021ZD0140300 to C.X.)+2 种基金Natural Science Foundation of Hainan Province(No.822RC703 for J.L.)Foundation of Hainan Educational Committee(No.Hnky2022-27 for J.L.)Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.,E36CWGBR24B and E36CZG14132 to T.C.)。
文摘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.
基金National Natural Science Foundation of China(31640001 and T2350005 to C.X.)Ministry of Science and Technology of China(2021ZD0140300 to C.X.)Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.,E36CWGBR24B and E36CZG14132 to T.C.)。
文摘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.
基金supported by the National Natural Science Foundation of China(31640001 to C.X.,U21A20148 to X.Z.and C.X.)the Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.)。
文摘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.
基金supported by the National Natural Science Foundation of China(31640001 and T2350005 to C.X.,U21A20148 to X.Z.and C.X.)Ministry of Science and Technology of China(2021ZD0140300 to C.X.)Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.,E36CWGBR24B and E36CZG14132 to T.C.)。
文摘The morphology is the consequence of evolution and adaptation.Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5μm long and 0.5μm wide.Many shape-related genes have been identified and used in morphology engineering of this bacteria.However,little is known about if specific metabolism and metal irons could modulate bacteria morphology.Here in this study,we discovered filamentous shape change of E.coli cells overexpressing pigeon MagR,a putative magnetoreceptor and extremely conserved iron-sulfur protein.Comparative transcriptomic analysis strongly suggested that the iron metabolism change and iron accumulation due to the overproduction of MagR was the key to the morphological change.This model was further validated,and filamentous morphological change was also achieved by supplement E.coli cells with iron in culture medium or by increase the iron uptake genes such as entB and fepA.Our study extended our understanding of morphology regulation of bacteria,and may also serves as a prototype of morphology engineering by modulating the iron metabolism.
基金supported by the National Natural Science Foundation of China (31572349, 31272396) to Yuequn Wangthe China Scholarship Council (201406720012) to Xiyang Peng+1 种基金the Cooperative Innovation Center of Engineering and New Products for Developmental Biology of Hunan Province (2013-448-6)the National Research Foundation of Singapore (NRF-CRP7-2010-03) to Yunhan Hong
文摘Magnetoreception is essential for magnetic orientation in animal migration. The molecular basis for magnetoreception has re- cently been elucidated in fruitfly as complexes between the magnetic receptor magnetoreceptor （MagR） and its ligand crypto- chrome （Cry）. MagR and Cry are present in the animal kingdom. However, it is unknown whether they perform a conserved role in diverse animals. Here we report the identification and expression of zebrafish MagR and Cry homologs towards under- standing their roles in lower vertebrates. A single rnagr gene and 7 cry genes are present in the zebrafish genome. Zebrafish has four cryl genes （crylaa, crylab, crylba and cry]bb） homologous to human CRY1 and a single ortholog of human CRY2 as well as 2 cry-like genes （cry4 and cryS）. By RT-PCR, magr exhibited a high level of ubiquitous RNA expression in embryos and adult organs, whereas cry genes displayed differential embryonic and adult expression. Importantly, magr depletion did not produce apparent abnormalities in organogenesis. Taken together, magr and cry2 exist as a single copy gene, whereas cryl exists as multiple gene duplicates in zebrafish. Our result suggests that magr may play a dispensable role in organogenesis and predicts a possibility to generate rnagr mutants for analyzing its role in zebrafish.
基金supported by Tsinghua-Peking Center for Life SciencesIDG/Mc Govern Foundationthe National Natural Science Foundation of China
文摘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.
基金supported by the National Research Foundation of Singapore(NRF-CRP7-2010-03)
文摘Magnetoreception is a hallmark ability of animals for orientation and migration via sensing and utilizing geomagnetic fields.Magnetoreceptor(MagR) and cryptochromes(Cry) have recently been identified as the basis for magnetoreception in Drosophila.However,it has remained unknown whether MagR and Cry have conserved roles in diverse animals.Here we report the identification and expression of magr and cry genes in the fish medaka(Oryzias latipes).Cloning and sequencing identified a single magr gene,four cry genes and one cry-like gene in medaka.By sequence alignment,chromosomal synteny and gene structure analysis,medaka cry2 and magr were found to be the orthologs of human Cry2 and Magr,with cry1 aa and crylab being coorthologs of human Cry1.Therefore,magr and cry2 have remained as single copy genes,whereas cry1 has undergone two rounds of gene duplication in medaka.Interestingly,magr and cry genes were detected in various stages throughout embryogenesis and displayed ubiquitous expression in adult organs rather than specific or preferential expression in neural organs such as brain and eye.Importantly,magr knockdown by morpholino did not produce visible abnormality in developing embryos,pointing to the possibility of producing viable magr knockouts in medaka as a vertebrate model for magnet biology.
