Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual＇s level of intelligence,emotional state and mental health.Changes in the structure and efficacy of synaps...Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual＇s level of intelligence,emotional state and mental health.Changes in the structure and efficacy of synapses are the biological basis of learning and memory.However,investigation of the molecular architecture of synapses has been impeded by the lack of efficient techniques with sufficient resolution.Recent developments in state-of-the-art nano-imaging techniques have opened up a new window for dissecting the molecular organization of neuronal synapses with unprecedented resolution.Here,we review recent technological advances in nano-imaging techniques as well as their applications to the study of synapses,emphasizing super-resolution light microscopy and 3-dimensional electron tomography.展开更多
Mediator is a highly conserved large protein complex(25 proteins,>1000 kD a)and preeminently responsible for eu-karyotic transcription,which contains a dissociable‘Cdk8 module’.Although increasing evidence demons...Mediator is a highly conserved large protein complex(25 proteins,>1000 kD a)and preeminently responsible for eu-karyotic transcription,which contains a dissociable‘Cdk8 module’.Although increasing evidence demonstrates that Cdk8 module plays both positive and negative roles in transcription regulation,the detailed structure,and subu-nit organization,molecular mechanism how it regulates transcription remain elusive.Here we used single-particle electron microscopy to characterize the structure and subunit organization of the Cdk8 module and illuminated the substantial mobility of the Med13 subunit results in the structural fl exibility.The Cdk8 module interaction with core Mediator is concurrent with active transcription in vivo.An interaction with the Cdk8 module induces core Mediator into very extended conformation in vitro,which is presumed to be an active functional state of Mediator.Taken together,our results illuminated the detailed archi-tecture of Cdk8 module,and suggested the Cdk8 module could positively regulate transcription by modulating Me-diator conformation.展开更多
基金supported by grants from the National Natural Science Foundation of China (30725017 and 30928003)MOST (2009CB941300)
文摘Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual＇s level of intelligence,emotional state and mental health.Changes in the structure and efficacy of synapses are the biological basis of learning and memory.However,investigation of the molecular architecture of synapses has been impeded by the lack of efficient techniques with sufficient resolution.Recent developments in state-of-the-art nano-imaging techniques have opened up a new window for dissecting the molecular organization of neuronal synapses with unprecedented resolution.Here,we review recent technological advances in nano-imaging techniques as well as their applications to the study of synapses,emphasizing super-resolution light microscopy and 3-dimensional electron tomography.
基金This work was supported by grants from the National Basic Research Program(973 Program)(No.2013CB910200)the National Natural Science Foundation of China(Grant Nos.31170694 and 31222017)+1 种基金Ministry of Education of PRC(NCET-11-0874)Chinese Academy Of Sciences(48500108-6).
文摘Mediator is a highly conserved large protein complex(25 proteins,>1000 kD a)and preeminently responsible for eu-karyotic transcription,which contains a dissociable‘Cdk8 module’.Although increasing evidence demonstrates that Cdk8 module plays both positive and negative roles in transcription regulation,the detailed structure,and subu-nit organization,molecular mechanism how it regulates transcription remain elusive.Here we used single-particle electron microscopy to characterize the structure and subunit organization of the Cdk8 module and illuminated the substantial mobility of the Med13 subunit results in the structural fl exibility.The Cdk8 module interaction with core Mediator is concurrent with active transcription in vivo.An interaction with the Cdk8 module induces core Mediator into very extended conformation in vitro,which is presumed to be an active functional state of Mediator.Taken together,our results illuminated the detailed archi-tecture of Cdk8 module,and suggested the Cdk8 module could positively regulate transcription by modulating Me-diator conformation.
