AMPA Receptor and PET Tracer Limitation.The alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor(AMPAR)is a subtype of ionotropic glutamate receptor.It functions as a ligand-gated ion channel and is primar...AMPA Receptor and PET Tracer Limitation.The alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor(AMPAR)is a subtype of ionotropic glutamate receptor.It functions as a ligand-gated ion channel and is primarily responsible for rapidly transmitting the signal from glutamate in the central nervous system[1].This receptor plays a crucial role in various cognitive functions including learning,memory,cognition,synaptic plasticity,and neurodevelopment.AMPARs are typically composed of four subunits,namely GluA1,GluA2,GluA3,and GluA4,which can form homo-or hetero-tetramers.These subunits bind directly or indirectly to various scaffolding proteins such as transmembrane AMPA receptor regulatory proteins(TARPs).展开更多
The CC chemokine ligand 2(CCL2,also known as MCP-1)and its cognate receptor CCR2 have wellcharacterized roles in chemotaxis.CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excit...The CC chemokine ligand 2(CCL2,also known as MCP-1)and its cognate receptor CCR2 have wellcharacterized roles in chemotaxis.CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability.However,the detailed molecular mechanism underlying this process remains largely unclear.In cultured hippocampal neurons,CCL2 application rapidly upregulated surface expression of GluA1,in a CCR2-dependent manner,assayed using SEP-GluA1 live imaging,surface GluA1 antibody staining,and electrophysiology.Using pharmacology and reporter assays,we further showed that CCL2 upregulated surface GluA1 expression primarily via Gαq-and CaMKII-dependent signaling.Consistently,using i.p.injection of lipopolysaccharide to induce neuroinflammation,we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus,an effect blocked in Ccr2−/−mice.Together,these results provide a mechanism through which CCL2,and other secreted molecules that signal through G-protein coupled receptors,can directly regulate synaptic transmission.展开更多
基金supported by the National Natural Science Foundation of China(32371066)the Guangdong Basic and Applied Basic Research Foundation(2022A1515010134)+1 种基金the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019009)the Shenzhen Technological Research Center for Primate Translational Medicine(XMHT20220104005).
文摘AMPA Receptor and PET Tracer Limitation.The alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor(AMPAR)is a subtype of ionotropic glutamate receptor.It functions as a ligand-gated ion channel and is primarily responsible for rapidly transmitting the signal from glutamate in the central nervous system[1].This receptor plays a crucial role in various cognitive functions including learning,memory,cognition,synaptic plasticity,and neurodevelopment.AMPARs are typically composed of four subunits,namely GluA1,GluA2,GluA3,and GluA4,which can form homo-or hetero-tetramers.These subunits bind directly or indirectly to various scaffolding proteins such as transmembrane AMPA receptor regulatory proteins(TARPs).
基金supported by grants from the National Natural Science Foundation of China(32030049 and 82101619)the Ministry of Science and Technology of China(2021ZD0202500)+1 种基金the Key-Area Research and Development Program of Guangdong Province(2019B030335001)the Qidong-SLS Innovation Fund(to X.Y.)。
文摘The CC chemokine ligand 2(CCL2,also known as MCP-1)and its cognate receptor CCR2 have wellcharacterized roles in chemotaxis.CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability.However,the detailed molecular mechanism underlying this process remains largely unclear.In cultured hippocampal neurons,CCL2 application rapidly upregulated surface expression of GluA1,in a CCR2-dependent manner,assayed using SEP-GluA1 live imaging,surface GluA1 antibody staining,and electrophysiology.Using pharmacology and reporter assays,we further showed that CCL2 upregulated surface GluA1 expression primarily via Gαq-and CaMKII-dependent signaling.Consistently,using i.p.injection of lipopolysaccharide to induce neuroinflammation,we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus,an effect blocked in Ccr2−/−mice.Together,these results provide a mechanism through which CCL2,and other secreted molecules that signal through G-protein coupled receptors,can directly regulate synaptic transmission.
