Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3.
Synaptic receptors gate the neuronal response to incoming signals, but they are not homogeneously distributed on dendrites. A spatially defined receptor distribution can preferentially amplify certain synaptic inputs, resize receptive fields of neurons, and optimize information processing within a neuronal circuit. Thus, a longstanding question is how the spatial organization of synaptic receptors is achieved. Here, we find that action potentials provide local signals that influence the distribution of synaptic AMPA receptors along dendrites in mouse cerebellar stellate cells. Graded dendritic depolarizations elevate CPEB3 protein at proximal dendrites, where we suggest that CPEB3 binds to GluA2 mRNA, suppressing GluA2 protein synthesis leading to a distance-dependent increase in synaptic GluA2 AMPARs. The activity-induced expression of CPEB3 requires increased Ca(2+) and PKC activation. Our results suggest a cell-autonomous mechanism where sustained postsynaptic firing drives graded local protein synthesis, thus directing the spatial organization of synaptic AMPARs.
Department of Cell Biology and Anatomy, LSU Health Sciences Center, New Orleans, LA 70112, USA; Department of Biology, Penn State University, State College, PA 16802, USA.
Iaroslav
I
Savtchouk
Department of Cell Biology and Anatomy, LSU Health Sciences Center, New Orleans, LA 70112, USA; Department of Biology, Penn State University, State College, PA 16802, USA.
Lu
L
Sun
Department of Cell Biology and Anatomy, LSU Health Sciences Center, New Orleans, LA 70112, USA.
Crhistian L
CL
Bender
Department of Cell Biology and Anatomy, LSU Health Sciences Center, New Orleans, LA 70112, USA.
Qian
Q
Yang
Laboratory of Molecular Biology and Genetics, Institute of Experimental Medicine, 1450 Budapest, Hungary.
Gábor
G
Szabó
Department of Cell Biology and Anatomy, LSU Health Sciences Center, New Orleans, LA 70112, USA; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, USA.
Sonia
S
Gasparini
Department of Cell Biology and Anatomy, LSU Health Sciences Center, New Orleans, LA 70112, USA; Department of Biology, Penn State University, State College, PA 16802, USA. Electronic address: sliu@lsuhsc.edu.
Siqiong June
SJ
Liu
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008867:Microtomy; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D046509:Tissue Culture Techniques
C477603:Cpeb3 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D011493:Protein Kinase C; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium
AMPA receptor; CPEB3; GluA2; PKC; action potentials; calcium imaging; cerebellar stellate cell; dendritic gradient; subunit composition; topostatic plasticity
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