Trans-synaptic Eph receptor-ephrin signaling in hippocampal mossy fiber LTP.
The site of induction of long-term potentiation (LTP) at mossy fiber-CA3 synapses in the hippocampus is unresolved, with data supporting both pre- and postsynaptic mechanisms. Here we report that mossy fiber LTP was reduced by perfusion of postsynaptic neurons with peptides and antibodies that interfere with binding of EphB receptor tyrosine kinases (EphRs) to the PDZ protein GRIP. Mossy fiber LTP was also reduced by extracellular application of soluble forms of B-ephrins, which are normally membrane-anchored presynaptic ligands for the EphB receptors. The application of soluble ligands for presynaptic ephrins increased basal excitatory transmission and occluded both tetanus and forskolin-induced synaptic potentiation. These findings suggest that PDZ interactions in the postsynaptic neuron and trans-synaptic interactions between postsynaptic EphB receptors and presynaptic B-ephrins are necessary for the induction of mossy fiber LTP.
Contractor
Anis
A
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. contractor@salk.edu
Rogers
Cheryl
C
Maron
Cornelia
C
Henkemeyer
Mark
M
Swanson
Geoffrey T
GT
Heinemann
Stephen F
SF
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D036387:Ephrin-B1; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D008024:Ligands; D017774:Long-Term Potentiation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D036141:Receptor, EphA7; D036183:Receptor, EphB2; D018091:Receptors, AMPA / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D036387:Ephrin-B1; C491309:Grip1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; D005576:Colforsin; D020794:Receptor Protein-Tyrosine Kinases; D036141:Receptor, EphA7; D036183:Receptor, EphB2; D017868:Cyclic AMP-Dependent Protein Kinases; C104722:glutamate receptor ionotropic, AMPA 2