Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling.
Communication between glial cells and neurons is emerging as a critical parameter of synaptic function. However, the molecular mechanisms underlying the ability of glial cells to modify synaptic structure and physiology are poorly understood. Here we describe a repulsive interaction that regulates postsynaptic morphology through the EphA4 receptor tyrosine kinase and its ligand ephrin-A3. EphA4 is enriched on dendritic spines of pyramidal neurons in the adult mouse hippocampus, and ephrin-A3 is localized on astrocytic processes that envelop spines. Activation of EphA4 by ephrin-A3 was found to induce spine retraction, whereas inhibiting ephrin/EphA4 interactions distorted spine shape and organization in hippocampal slices. Furthermore, spine irregularities in pyramidal neurons from EphA4 knockout mice and in slices transfected with kinase-inactive EphA4 indicated that ephrin/EphA4 signaling is critical for spine morphology. Thus, our data support a model in which transient interactions between the ephrin-A3 ligand and the EphA4 receptor regulate the structure of excitatory synaptic connections through neuroglial cross-talk.
Murai
Keith K
KK
The Burnham Institute, Neurobiology Program, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Nguyen
Louis N
LN
Irie
Fumitoshi
F
Yamaguchi
Yu
Y
Pasquale
Elena B
EB
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D002450:Cell Communication / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D036384:Ephrin-A3 / Q000235:genetics / Q000378:metabolism*; D036387:Ephrin-B1 / Q000378:metabolism / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000002:abnormalities / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics; D010770:Phosphotransferases / Q000172:deficiency / Q000235:genetics; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D036122:Receptor, EphA4 / Q000172:deficiency* / Q000235:genetics; D036081:Receptors, Eph Family / Q000187:drug effects / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*
D036384:Ephrin-A3; D036387:Ephrin-B1; D011993:Recombinant Fusion Proteins; D010770:Phosphotransferases; D036122:Receptor, EphA4; D036081:Receptors, Eph Family