Tyrosine phosphorylation sites in ephrinB2 are required for hippocampal long-term potentiation but not long-term depression.
Standard
Tyrosine phosphorylation sites in ephrinB2 are required for hippocampal long-term potentiation but not long-term depression. / Bouzioukh, Farima; Wilkinson, George A; Adelmann, Giselind; Frotscher, Michael; Stein, Valentin; Klein, Rüdiger.
In: J NEUROSCI, Vol. 27, No. 42, 42, 2007, p. 11279-11288.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Tyrosine phosphorylation sites in ephrinB2 are required for hippocampal long-term potentiation but not long-term depression.
AU - Bouzioukh, Farima
AU - Wilkinson, George A
AU - Adelmann, Giselind
AU - Frotscher, Michael
AU - Stein, Valentin
AU - Klein, Rüdiger
PY - 2007
Y1 - 2007
N2 - Long-lasting changes in synaptic function are thought to be the cellular basis for learning and memory and for activity-dependent plasticity during development. Long-term potentiation (LTP) and long-term depression (LTD) are two opposing forms of synaptic plasticity that help fine tune neural connections and possibly serve to store information in the brain. Eph receptor tyrosine kinases and their transmembrane ligands, the ephrinBs, have essential roles in certain forms of synaptic plasticity. At the CA3-CA1 hippocampal synapse, EphB2 and EphA4 receptors are critically involved in long-term plasticity independent of their cytoplasmic domains, suggesting that ephrinBs are the active signaling partners. In cell-based assays, ephrinB reverse signaling was previously shown to involve phosphotyrosine-dependent and postsynaptic density-95/Discs large/zona occludens-1 (PDZ) domain interaction-dependent pathways. Which reverse signaling mode is required at hippocampal synapses is unknown. To address this question, we used knock-in mice expressing mutant isoforms of ephrinB2 that are deficient in specific aspects of reverse signaling. Our analysis revealed that tyrosine phosphorylation sites in ephrinB2 are required to mediate normal hippocampal LTP, but not for LTD. Conversely, ephrinB2 lacking the C-terminal PDZ interaction site, but competent to undergo tyrosine phosphorylation, cannot mediate either form of long-term plasticity. Our results provide the first evidence for phosphotyrosine-dependent ephrinB reverse signaling in a neuronal network and for differential ephrinB2 reverse signaling in two forms of synaptic plasticity.
AB - Long-lasting changes in synaptic function are thought to be the cellular basis for learning and memory and for activity-dependent plasticity during development. Long-term potentiation (LTP) and long-term depression (LTD) are two opposing forms of synaptic plasticity that help fine tune neural connections and possibly serve to store information in the brain. Eph receptor tyrosine kinases and their transmembrane ligands, the ephrinBs, have essential roles in certain forms of synaptic plasticity. At the CA3-CA1 hippocampal synapse, EphB2 and EphA4 receptors are critically involved in long-term plasticity independent of their cytoplasmic domains, suggesting that ephrinBs are the active signaling partners. In cell-based assays, ephrinB reverse signaling was previously shown to involve phosphotyrosine-dependent and postsynaptic density-95/Discs large/zona occludens-1 (PDZ) domain interaction-dependent pathways. Which reverse signaling mode is required at hippocampal synapses is unknown. To address this question, we used knock-in mice expressing mutant isoforms of ephrinB2 that are deficient in specific aspects of reverse signaling. Our analysis revealed that tyrosine phosphorylation sites in ephrinB2 are required to mediate normal hippocampal LTP, but not for LTD. Conversely, ephrinB2 lacking the C-terminal PDZ interaction site, but competent to undergo tyrosine phosphorylation, cannot mediate either form of long-term plasticity. Our results provide the first evidence for phosphotyrosine-dependent ephrinB reverse signaling in a neuronal network and for differential ephrinB2 reverse signaling in two forms of synaptic plasticity.
KW - Animals
KW - Humans
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Long-Term Synaptic Depression physiology
KW - Long-Term Potentiation physiology
KW - Hippocampus metabolism
KW - Binding Sites physiology
KW - Hela Cells
KW - Neuronal Plasticity physiology
KW - Phosphorylation
KW - Receptor, EphB2 genetics
KW - Tyrosine genetics
KW - Animals
KW - Humans
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Long-Term Synaptic Depression physiology
KW - Long-Term Potentiation physiology
KW - Hippocampus metabolism
KW - Binding Sites physiology
KW - Hela Cells
KW - Neuronal Plasticity physiology
KW - Phosphorylation
KW - Receptor, EphB2 genetics
KW - Tyrosine genetics
M3 - SCORING: Zeitschriftenaufsatz
VL - 27
SP - 11279
EP - 11288
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 42
M1 - 42
ER -