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The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation

Jiang, Sunny Zhihong ; Shahoha, Meishar ; Zhang, Hai-Ying ; Brancaleone, William ; Elkahloun, Abdel ; Tejeda, Hugo A. ; Ashery, Uri ; Eiden, Lee E.

Cellular and molecular life sciences : CMLS, 2024-12, Vol.81 (1), p.48-48, Article 48 [Periódico revisado por pares]

Cham: Springer International Publishing

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Título:
The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation
Autor: Jiang, Sunny Zhihong ; Shahoha, Meishar ; Zhang, Hai-Ying ; Brancaleone, William ; Elkahloun, Abdel ; Tejeda, Hugo A. ; Ashery, Uri ; Eiden, Lee E.
Assuntos: Ablation ; Amygdala ; Animals ; Associative learning ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Brain slice preparation ; c-Fos protein ; Cell Biology ; Cognitive ability ; Constraints ; Context ; Cyclic AMP ; Dentate gyrus ; Early Growth Response Protein 1 - genetics ; EGR-1 protein ; Extracellular signal-regulated kinase ; Fear ; Fear conditioning ; Genes, Immediate-Early ; Guanine nucleotide exchange factor ; Guanine Nucleotide Exchange Factors - genetics ; Hippocampus ; Kinases ; Learning ; Life Sciences ; Long-term potentiation ; MAP kinase ; Memory ; Mental disorders ; Mice ; Neural plasticity ; Nucleotides ; Original ; Original Article ; Proto-Oncogene Proteins c-fos ; Risk factors ; Schizophrenia ; Signal Transduction ; Synapses ; Tonic immobility
É parte de: Cellular and molecular life sciences : CMLS, 2024-12, Vol.81 (1), p.48-48, Article 48
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Descrição: The MAP kinase ERK is important for neuronal plasticity underlying associative learning, yet specific molecular pathways for neuronal ERK activation are undetermined. RapGEF2 is a neuron-specific cAMP sensor that mediates ERK activation. We investigated whether it is required for cAMP-dependent ERK activation leading to other downstream neuronal signaling events occurring during associative learning, and if RapGEF2-dependent signaling impairments affect learned behavior. Camk2α-cre +/- ::RapGEF2 fl/fl mice with depletion of RapGEF2 in hippocampus and amygdala exhibit impairments in context- and cue-dependent fear conditioning linked to corresponding impairment in Egr1 induction in these two brain regions. Camk2α-cre +/- ::RapGEF2 fl/fl mice show decreased RapGEF2 expression in CA1 and dentate gyrus associated with abolition of pERK and Egr1, but not of c-Fos induction, following fear conditioning, impaired freezing to context after fear conditioning, and impaired cAMP-dependent long-term potentiation at perforant pathway and Schaffer collateral synapses in hippocampal slices ex vivo. RapGEF2 expression is largely eliminated in basolateral amygdala, also involved in fear memory, in Camk2α-cre +/- ::RapGEF2 fl/fl mice. Neither Egr1 nor c-fos induction in BLA after fear conditioning, nor cue-dependent fear learning, are affected by ablation of RapGEF2 in BLA. However, Egr1 induction (but not that of c-fos) in BLA is reduced after restraint stress-augmented fear conditioning, as is freezing to cue after restraint stress-augmented fear conditioning, in Camk2α-cre +/- ::RapGEF2 fl/fl mice. Cyclic AMP-dependent GEFs have been genetically associated as risk factors for schizophrenia, a disorder associated with cognitive deficits. Here we show a functional link between one of them, RapGEF2, and cognitive processes involved in associative learning in amygdala and hippocampus.
Editor: Cham: Springer International Publishing
Idioma: Inglês

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The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation

Jiang, Sunny Zhihong ; Shahoha, Meishar ; Zhang, Hai-Ying ; Brancaleone, William ; Elkahloun, Abdel ; Tejeda, Hugo A. ; Ashery, Uri ; Eiden, Lee E.

Cham: Springer International Publishing

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