With the development of computational methods and RNA sequencing technology for assembling the transcriptome, it is becoming clear that the mammal genome is pervasively tran- scribed, and large numbers of long noncodi...With the development of computational methods and RNA sequencing technology for assembling the transcriptome, it is becoming clear that the mammal genome is pervasively tran- scribed, and large numbers of long noncoding RNAs （lncRNAs） composing the major part of the transcriptome have been identified （Ravasi et al., 2006; Birney et al., 2007;展开更多
In the past two decades,various super-resolution(SR)microscopy techniques have been developed to break the di®raction limit using subdi®raction excitation to spatially modulate the°uorescence emission.P...In the past two decades,various super-resolution(SR)microscopy techniques have been developed to break the di®raction limit using subdi®raction excitation to spatially modulate the°uorescence emission.Photomodulatable°uorescent proteins(FPs)can be activated by light of speci¯c wavelengths to produce either stochastic or patterned subdi®raction excitation,resulting in improved optical resolution.In this review,we focus on the recently developed photomodulatable FPs or commonly used SR microscopies and discuss the concepts and strategies for optimizing and selecting the biochemical and photophysical properties of PMFPs to improve the spatiotemporal resolution of SR techniques,especially time-lapse live-cell SR techniques.展开更多
Apparently,the genomes of many organisms are pervasively transcribed,and long noncoding RNAs(lncRNAs)make up the majority of cellular transcripts.LncRNAs have been reported to play important roles in many biological p...Apparently,the genomes of many organisms are pervasively transcribed,and long noncoding RNAs(lncRNAs)make up the majority of cellular transcripts.LncRNAs have been reported to play important roles in many biological processes;however,their effects on locomotion are poorly understood.Here,we presented a novel lncRNA,Locomotion Regulatory Gene(LRG),which participates in locomotion by sequestering Synaptotagmin 1(SYT1).LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body,motoneuron or muscle-expression of LRG.At the molecular level,the synaptic vesicles(SVs)release and movement-related SYT1 protein was recognized as LRG-interacting protein candidate.Furthermore,LRG had no effects on SYT1 expression.Genetically,the behavioral defects in LRG mutant could be rescued by pan-neuronal knock-down of Syt1.Taken together,all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its expression.Our work displays a new function of lncRNA and provides insights for revealing the pathogenesis of neurological diseases with motor disorders.展开更多
Rational protein design is a powerful strategy,not only for revealing the structure and function relationship of natural metalloproteins,but also for creating artificial metalloproteins with improved properties and fu...Rational protein design is a powerful strategy,not only for revealing the structure and function relationship of natural metalloproteins,but also for creating artificial metalloproteins with improved properties and functions.Myoglobin(Mb),a small heme protein created by nature with diverse functions,has been shown to be an ideal scaffold for rational protein design.The progress reviewed herein includes fine-tuning its native functions of O2binding and transport,peroxidase activity and nitrite reductase(NIR)activity,and rational expanding its functionalities to peroxygenase,heme-copper oxidase(HCO),nitric oxide reductase(NOR),as well as hydroxylamine reductase.These studies have enhanced our understanding of how metalloproteins work in nature,and provided insights for rational design of functional metalloproteins for practical applications in the future.展开更多
Nematode sperm undergo a drastic physiological change during spermiogenesis(sperm activation).Unlike mammalian flagellated sperm,nematode sperm are amoeboid cells and their motility is driven by the dynamics of a cyto...Nematode sperm undergo a drastic physiological change during spermiogenesis(sperm activation).Unlike mammalian flagellated sperm,nematode sperm are amoeboid cells and their motility is driven by the dynamics of a cytoskeleton composed of major sperm protein(MSP)rather than actin found in other crawling cells.This review focuses on sperm from Caenorhabditis elegans and Ascaris suum to address the roles of external and internal factors that trigger sperm activation and power sperm motility.Nematode sperm can be activated in vitro by several factors,including Pronase and ionophores,and in vivo through the TRY-5 and SPE-8 pathways.Moreover,protease and protease inhibitors are crucial regulators of sperm maturation.MSP-based sperm motility involves a coupled process of protrusion and retraction,both of which have been reconstituted in vitro.Sperm motility is mediated by phosphorylation signals,as illustrated by identification of several key components(MPOP,MFPs and MPAK)in Ascaris and the characterization of GSP-3/4 in C.elegans.展开更多
The dynamic polar polymers actin fi laments and microtu-bules are usually employed to provide the structural ba-sis for establishing cell polarity in most eukaryotic cells.Radially round and immotile spermatids from n...The dynamic polar polymers actin fi laments and microtu-bules are usually employed to provide the structural ba-sis for establishing cell polarity in most eukaryotic cells.Radially round and immotile spermatids from nematodes contain almost no actin or tubulin,but still have the abil-ity to break symmetry to extend a pseudopod and initiate the acquisition of motility powered by the dynamics of cytoskeleton composed of major sperm protein(MSP)during spermiogenesis(sperm activation).However,the signal transduction mechanism of nematode sperm activation and motility acquisition remains poorly under-stood.Here we show that Ca^(2+) oscillations induced by the Ca^(2+) release from intracellular Ca^(2+) store through inositol(1,4,5)-trisphosphate receptor are required for Ascaris suum sperm activation.The chelation of cytosolic Ca^(2+) suppresses the generation of a functional pseudopod,and this suppression can be relieved by introducing ex-ogenous Ca^(2+) into sperm cells.Ca^(2+) promotes MSP-based sperm motility by increasing mitochondrial membrane potential and thus the energy supply required for MSP cytoskeleton assembly.On the other hand,Ca^(2+) promotes MSP disassembly by activating Ca^(2+)/calmodulin-depend-ent serine/threonine protein phosphatase calcineurin.In addition,Ca^(2+)/camodulin activity is required for the fusion of sperm-specifi c membranous organelle with the plasma membrane,a regulated exocytosis required for sperm mo-tility.Thus,Ca^(2+)plays multifunctional roles during sperm activation in Ascaris suum.展开更多
基金supported by the grants from the National Natural Science Foundation of China (No. 31300889)
文摘With the development of computational methods and RNA sequencing technology for assembling the transcriptome, it is becoming clear that the mammal genome is pervasively tran- scribed, and large numbers of long noncoding RNAs （lncRNAs） composing the major part of the transcriptome have been identified （Ravasi et al., 2006; Birney et al., 2007;
基金This project was supported by the National Basic Research Program (2013CB910103)the National Natural Science Foundation of China (Grant Nos.31421002,31370851 and 31300612)+1 种基金the Project of the Chinese Academy of Sciences (XDB08030202)the Beijing Natural Science Foundation (7131011)。
文摘In the past two decades,various super-resolution(SR)microscopy techniques have been developed to break the di®raction limit using subdi®raction excitation to spatially modulate the°uorescence emission.Photomodulatable°uorescent proteins(FPs)can be activated by light of speci¯c wavelengths to produce either stochastic or patterned subdi®raction excitation,resulting in improved optical resolution.In this review,we focus on the recently developed photomodulatable FPs or commonly used SR microscopies and discuss the concepts and strategies for optimizing and selecting the biochemical and photophysical properties of PMFPs to improve the spatiotemporal resolution of SR techniques,especially time-lapse live-cell SR techniques.
基金supported by grants from National Natural Science Foundation of China(31571033,32220103007)Major Program of the National Natural Science Foundation of China(T2293720/T2293722)Strategic Priority Research Program of Chinese Academy of Sciences(XDB37030303)。
文摘Apparently,the genomes of many organisms are pervasively transcribed,and long noncoding RNAs(lncRNAs)make up the majority of cellular transcripts.LncRNAs have been reported to play important roles in many biological processes;however,their effects on locomotion are poorly understood.Here,we presented a novel lncRNA,Locomotion Regulatory Gene(LRG),which participates in locomotion by sequestering Synaptotagmin 1(SYT1).LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body,motoneuron or muscle-expression of LRG.At the molecular level,the synaptic vesicles(SVs)release and movement-related SYT1 protein was recognized as LRG-interacting protein candidate.Furthermore,LRG had no effects on SYT1 expression.Genetically,the behavioral defects in LRG mutant could be rescued by pan-neuronal knock-down of Syt1.Taken together,all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its expression.Our work displays a new function of lncRNA and provides insights for revealing the pathogenesis of neurological diseases with motor disorders.
基金supported by the National Natural Science Foundation of China(21101091,31370812)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education of China.J.Wang is supported by the National Basic Research Program of China(2010CB912301,2009CB82 5505)+1 种基金the National Natural Science Foundation of China(90913022)Y.Lu is supported by the US National Institute of Health(GM062211)
文摘Rational protein design is a powerful strategy,not only for revealing the structure and function relationship of natural metalloproteins,but also for creating artificial metalloproteins with improved properties and functions.Myoglobin(Mb),a small heme protein created by nature with diverse functions,has been shown to be an ideal scaffold for rational protein design.The progress reviewed herein includes fine-tuning its native functions of O2binding and transport,peroxidase activity and nitrite reductase(NIR)activity,and rational expanding its functionalities to peroxygenase,heme-copper oxidase(HCO),nitric oxide reductase(NOR),as well as hydroxylamine reductase.These studies have enhanced our understanding of how metalloproteins work in nature,and provided insights for rational design of functional metalloproteins for practical applications in the future.
基金supported by the National Basic Research Program of China(Nos.2012CB94502,2010CB912303)(to L.M.)the National Natural Science Foundation of China(Grant Nos.31171337 and 30971648)(to L.M.)+1 种基金Grant Nos.30871226 and 31071180(to Y.Z.)supported by the Chinese Academy of Sciences 100-Talents Program.
文摘Nematode sperm undergo a drastic physiological change during spermiogenesis(sperm activation).Unlike mammalian flagellated sperm,nematode sperm are amoeboid cells and their motility is driven by the dynamics of a cytoskeleton composed of major sperm protein(MSP)rather than actin found in other crawling cells.This review focuses on sperm from Caenorhabditis elegans and Ascaris suum to address the roles of external and internal factors that trigger sperm activation and power sperm motility.Nematode sperm can be activated in vitro by several factors,including Pronase and ionophores,and in vivo through the TRY-5 and SPE-8 pathways.Moreover,protease and protease inhibitors are crucial regulators of sperm maturation.MSP-based sperm motility involves a coupled process of protrusion and retraction,both of which have been reconstituted in vitro.Sperm motility is mediated by phosphorylation signals,as illustrated by identification of several key components(MPOP,MFPs and MPAK)in Ascaris and the characterization of GSP-3/4 in C.elegans.
基金the National Basic Research Program(973 Program)(Nos.2012CB945002 and 2010CB912303)and 31171337 from the Chinese government.
文摘The dynamic polar polymers actin fi laments and microtu-bules are usually employed to provide the structural ba-sis for establishing cell polarity in most eukaryotic cells.Radially round and immotile spermatids from nematodes contain almost no actin or tubulin,but still have the abil-ity to break symmetry to extend a pseudopod and initiate the acquisition of motility powered by the dynamics of cytoskeleton composed of major sperm protein(MSP)during spermiogenesis(sperm activation).However,the signal transduction mechanism of nematode sperm activation and motility acquisition remains poorly under-stood.Here we show that Ca^(2+) oscillations induced by the Ca^(2+) release from intracellular Ca^(2+) store through inositol(1,4,5)-trisphosphate receptor are required for Ascaris suum sperm activation.The chelation of cytosolic Ca^(2+) suppresses the generation of a functional pseudopod,and this suppression can be relieved by introducing ex-ogenous Ca^(2+) into sperm cells.Ca^(2+) promotes MSP-based sperm motility by increasing mitochondrial membrane potential and thus the energy supply required for MSP cytoskeleton assembly.On the other hand,Ca^(2+) promotes MSP disassembly by activating Ca^(2+)/calmodulin-depend-ent serine/threonine protein phosphatase calcineurin.In addition,Ca^(2+)/camodulin activity is required for the fusion of sperm-specifi c membranous organelle with the plasma membrane,a regulated exocytosis required for sperm mo-tility.Thus,Ca^(2+)plays multifunctional roles during sperm activation in Ascaris suum.
