The Experts below are selected from a list of 55881 Experts worldwide ranked by ideXlab platform
Fumin Tian - One of the best experts on this subject based on the ideXlab platform.
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male pheromones modulate Synaptic Transmission at the c elegans neuromuscular junction in a sexually dimorphic manner
eLife, 2021Co-Authors: Kangying Qian, Wanxin Zeng, Yue Hao, Xianting Zeng, Haowen Liu, Lili Chen, Fumin TianAbstract:The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The Synaptic Transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of Synaptic Transmission remains poorly understood. Here we show that in Caenorhabditis elegans, the male environment increases the hermaphrodite cholinergic Transmission at the neuromuscular junction (NMJ), which alters hermaphrodites' locomotion velocity and mating efficiency. We identify that the male-specific pheromones mediate this Synaptic Transmission modulation effect in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to the male pheromones specifically increases the accumulation of preSynaptic CaV2 calcium channels and clustering of postSynaptic acetylcholine receptors at cholinergic synapses of NMJ, which potentiates cholinergic Synaptic Transmission. Thus, our study demonstrates a circuit mechanism for Synaptic modulation and behavioral flexibility by sexual dimorphic pheromones.
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male pheromones modulate Synaptic Transmission at the c elegans neuromuscular junction in a sexually dimorphic manner
bioRxiv, 2021Co-Authors: Kangying Qian, Wanxin Zeng, Yue Hao, Xianting Zeng, Haowen Liu, Lili Chen, Fumin TianAbstract:SUMMARY The development of functional synapses in the nervous system is important for animal physiology and behaviors. The Synaptic Transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of Synaptic Transmission remains poorly understood. Here we show that in C. elegans, the male pheromone increases the hermaphrodite cholinergic Transmission at the neuromuscular junction (NMJ), which alters hermaphrodites’ locomotion velocity and mating efficiency in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to male pheromones specifically increases the accumulation of preSynaptic CaV2 calcium channels and clustering of postSynaptic receptors at cholinergic synapses of NMJ, which potentiates cholinergic Synaptic Transmission. Thus, our study demonstrates a circuit mechanism for Synaptic modulation by sexual dimorphic pheromones.
Yuko Fukata - One of the best experts on this subject based on the ideXlab platform.
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lgi1 adam22 maguk configures transSynaptic nanoalignment for Synaptic Transmission and epilepsy prevention
Proceedings of the National Academy of Sciences of the United States of America, 2021Co-Authors: Yuko Fukata, Xiumin Chen, Satomi Chiken, Yoko Hirano, Atsushi Yamagata, Hiroki Inahashi, Makoto Sanbo, Hiromi Sano, Teppei Goto, Masumi HirabayashiAbstract:Physiological functioning and homeostasis of the brain rely on finely tuned Synaptic Transmission, which involves nanoscale alignment between preSynaptic neurotransmitter-release machinery and postSynaptic receptors. However, the molecular identity and physiological significance of transSynaptic nanoalignment remain incompletely understood. Here, we report that epilepsy gene products, a secreted protein LGI1 and its receptor ADAM22, govern transSynaptic nanoalignment to prevent epilepsy. We found that LGI1-ADAM22 instructs PSD-95 family membrane-associated guanylate kinases (MAGUKs) to organize transSynaptic protein networks, including NMDA/AMPA receptors, Kv1 channels, and LRRTM4-Neurexin adhesion molecules. Adam22ΔC5/ΔC5 knock-in mice devoid of the ADAM22-MAGUK interaction display lethal epilepsy of hippocampal origin, representing the mouse model for ADAM22-related epileptic encephalopathy. This model shows less-condensed PSD-95 nanodomains, disordered transSynaptic nanoalignment, and decreased excitatory Synaptic Transmission in the hippocampus. Strikingly, without ADAM22 binding, PSD-95 cannot potentiate AMPA receptor-mediated Synaptic Transmission. Furthermore, forced coexpression of ADAM22 and PSD-95 reconstitutes nano-condensates in nonneuronal cells. Collectively, this study reveals LGI1-ADAM22-MAGUK as an essential component of transSynaptic nanoarchitecture for precise Synaptic Transmission and epilepsy prevention.
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the lgi1 adam22 protein complex in Synaptic Transmission and Synaptic disorders
Neuroscience Research, 2017Co-Authors: Yuko Fukata, Yuri Miyazaki, Norihiko Yokoi, Masaki FukataAbstract:Abstract Physiological functioning of the brain requires fine-tuned Synaptic Transmission, and its dysfunction causes various brain disorders such as autism, dementia, and epilepsy. It is therefore extremely important to identify and characterize key regulators of Synaptic function. In particular, disease-related Synaptic proteins, such as autism-related neurexin–neuroligin and psychiatric disorder-related NMDA receptor, have attracted considerable attention. Recent basic and clinical research has highlighted critical roles of a ligand–receptor complex, LGI1–ADAM22, in Synaptic Transmission and brain function, as mutations in the LGI1 gene cause autosomal dominant lateral temporal lobe epilepsy and autoantibodies to LGI1 cause limbic encephalitis which is characterized by memory loss and seizures. Here, we will review our current knowledge about LGI1 and ADAM22, and discuss their patho-physiological roles in Synaptic Transmission and Synaptic disorders.
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epilepsy related ligand receptor complex lgi1 and adam22 regulate Synaptic Transmission
Science, 2006Co-Authors: Yuko Fukata, Tsuyoshi Iwanaga, Roger A. Nicoll, Hillel Adesnik, David S Bredt, Masaki FukataAbstract:Abnormally synchronized Synaptic Transmission in the brain causes epilepsy. Most inherited forms of epilepsy result from mutations in ion channels. However, one form of epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF), is characterized by mutations in a secreted neuronal protein, LGI1. We show that ADAM22, a transmembrane protein that when mutated itself causes seizure, serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated Synaptic Transmission in hippocampal slices. The mutated form of LGI1 fails to bind to ADAM22. ADAM22 is anchored to the postSynaptic density by cytoskeletal scaffolds containing stargazin. These studies in rat brain indicate possible avenues for understanding human epilepsy.
Yue Hao - One of the best experts on this subject based on the ideXlab platform.
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male pheromones modulate Synaptic Transmission at the c elegans neuromuscular junction in a sexually dimorphic manner
eLife, 2021Co-Authors: Kangying Qian, Wanxin Zeng, Yue Hao, Xianting Zeng, Haowen Liu, Lili Chen, Fumin TianAbstract:The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The Synaptic Transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of Synaptic Transmission remains poorly understood. Here we show that in Caenorhabditis elegans, the male environment increases the hermaphrodite cholinergic Transmission at the neuromuscular junction (NMJ), which alters hermaphrodites' locomotion velocity and mating efficiency. We identify that the male-specific pheromones mediate this Synaptic Transmission modulation effect in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to the male pheromones specifically increases the accumulation of preSynaptic CaV2 calcium channels and clustering of postSynaptic acetylcholine receptors at cholinergic synapses of NMJ, which potentiates cholinergic Synaptic Transmission. Thus, our study demonstrates a circuit mechanism for Synaptic modulation and behavioral flexibility by sexual dimorphic pheromones.
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male pheromones modulate Synaptic Transmission at the c elegans neuromuscular junction in a sexually dimorphic manner
bioRxiv, 2021Co-Authors: Kangying Qian, Wanxin Zeng, Yue Hao, Xianting Zeng, Haowen Liu, Lili Chen, Fumin TianAbstract:SUMMARY The development of functional synapses in the nervous system is important for animal physiology and behaviors. The Synaptic Transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of Synaptic Transmission remains poorly understood. Here we show that in C. elegans, the male pheromone increases the hermaphrodite cholinergic Transmission at the neuromuscular junction (NMJ), which alters hermaphrodites’ locomotion velocity and mating efficiency in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to male pheromones specifically increases the accumulation of preSynaptic CaV2 calcium channels and clustering of postSynaptic receptors at cholinergic synapses of NMJ, which potentiates cholinergic Synaptic Transmission. Thus, our study demonstrates a circuit mechanism for Synaptic modulation by sexual dimorphic pheromones.
Wanxin Zeng - One of the best experts on this subject based on the ideXlab platform.
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male pheromones modulate Synaptic Transmission at the c elegans neuromuscular junction in a sexually dimorphic manner
eLife, 2021Co-Authors: Kangying Qian, Wanxin Zeng, Yue Hao, Xianting Zeng, Haowen Liu, Lili Chen, Fumin TianAbstract:The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The Synaptic Transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of Synaptic Transmission remains poorly understood. Here we show that in Caenorhabditis elegans, the male environment increases the hermaphrodite cholinergic Transmission at the neuromuscular junction (NMJ), which alters hermaphrodites' locomotion velocity and mating efficiency. We identify that the male-specific pheromones mediate this Synaptic Transmission modulation effect in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to the male pheromones specifically increases the accumulation of preSynaptic CaV2 calcium channels and clustering of postSynaptic acetylcholine receptors at cholinergic synapses of NMJ, which potentiates cholinergic Synaptic Transmission. Thus, our study demonstrates a circuit mechanism for Synaptic modulation and behavioral flexibility by sexual dimorphic pheromones.
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male pheromones modulate Synaptic Transmission at the c elegans neuromuscular junction in a sexually dimorphic manner
bioRxiv, 2021Co-Authors: Kangying Qian, Wanxin Zeng, Yue Hao, Xianting Zeng, Haowen Liu, Lili Chen, Fumin TianAbstract:SUMMARY The development of functional synapses in the nervous system is important for animal physiology and behaviors. The Synaptic Transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of Synaptic Transmission remains poorly understood. Here we show that in C. elegans, the male pheromone increases the hermaphrodite cholinergic Transmission at the neuromuscular junction (NMJ), which alters hermaphrodites’ locomotion velocity and mating efficiency in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to male pheromones specifically increases the accumulation of preSynaptic CaV2 calcium channels and clustering of postSynaptic receptors at cholinergic synapses of NMJ, which potentiates cholinergic Synaptic Transmission. Thus, our study demonstrates a circuit mechanism for Synaptic modulation by sexual dimorphic pheromones.
Masumi Hirabayashi - One of the best experts on this subject based on the ideXlab platform.
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lgi1 adam22 maguk configures transSynaptic nanoalignment for Synaptic Transmission and epilepsy prevention
Proceedings of the National Academy of Sciences of the United States of America, 2021Co-Authors: Yuko Fukata, Xiumin Chen, Satomi Chiken, Yoko Hirano, Atsushi Yamagata, Hiroki Inahashi, Makoto Sanbo, Hiromi Sano, Teppei Goto, Masumi HirabayashiAbstract:Physiological functioning and homeostasis of the brain rely on finely tuned Synaptic Transmission, which involves nanoscale alignment between preSynaptic neurotransmitter-release machinery and postSynaptic receptors. However, the molecular identity and physiological significance of transSynaptic nanoalignment remain incompletely understood. Here, we report that epilepsy gene products, a secreted protein LGI1 and its receptor ADAM22, govern transSynaptic nanoalignment to prevent epilepsy. We found that LGI1-ADAM22 instructs PSD-95 family membrane-associated guanylate kinases (MAGUKs) to organize transSynaptic protein networks, including NMDA/AMPA receptors, Kv1 channels, and LRRTM4-Neurexin adhesion molecules. Adam22ΔC5/ΔC5 knock-in mice devoid of the ADAM22-MAGUK interaction display lethal epilepsy of hippocampal origin, representing the mouse model for ADAM22-related epileptic encephalopathy. This model shows less-condensed PSD-95 nanodomains, disordered transSynaptic nanoalignment, and decreased excitatory Synaptic Transmission in the hippocampus. Strikingly, without ADAM22 binding, PSD-95 cannot potentiate AMPA receptor-mediated Synaptic Transmission. Furthermore, forced coexpression of ADAM22 and PSD-95 reconstitutes nano-condensates in nonneuronal cells. Collectively, this study reveals LGI1-ADAM22-MAGUK as an essential component of transSynaptic nanoarchitecture for precise Synaptic Transmission and epilepsy prevention.
