Eph家族蛋白在学习记忆中作用的研究进展
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摘要
作为大脑最基本和重要的功能之一,学习记忆始终是脑科学研究的热点领域。尽管相关研究已经取得了很大进展,但其具体机制尚不完全清楚。能产生促红细胞生成素的肝癌细胞(eryth-ropoietin-producing hepatocellular carcinoma cell,Eph)受体与其配体肝配蛋白被统称为Eph家族蛋白,其分布十分广泛且功能复杂。越来越多的研究表明,Eph家族蛋白能够调控包括突触发生及突触可塑性等多种细胞行为,在学习记忆中发挥不可或缺的作用。本文重点介绍Eph家族蛋白对学习记忆的作用并对其可能的作用机制进行概述。
引文
1 Nelson TJ,Alkon DL.Molecular regulation of synaptogenesis during associative learning and memory.Brain Res,2014,1621239~251.
2 Hruska M,Dalva MB.Ephrin regulation of synapse formation,function and plasticity.Mol Cell Neurosci,2012,5035~44.
3 Kania A,Klein R.Mechanisms of ephrin-Eph signalling in development,physiology and disease.Nat Rev Mol Cell Biol,2016,17240~256.
4 Monica D,Raphael L.The role of Ephs and ephrins in memory formation.Int J Neuropsychopharmacol,2016,19pyv106.
5 Dines M,Grinberg S,Vassiliev M,et al.The roles of Eph receptors in contextual fear conditioning memory formation.Neurobiol Learn Mem,2015,12462~70.
6 Alapin JM,Dines M,Vassiliev M,et al.Activation of Eph B2 forward signaling enhances memory consolidation.Cell Rep,2018,232014~2025.
7 Dines M,Lamprecht R.Ephrin A4 mimetic peptide targeted to Eph A binding site impairs the formation of long-term fear memory in lateral amygdala.Transl Psychiatry,2014,4e450.
8 Srivastava N,Robichaux MA,Chenaux G,et al.Eph B2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak.Mol Cell Neurosci,2013,52106~116.
9 Soskis MJ,Ho HY,Bloodgood BL,et al.A chemical genetic approach reveals distinct Eph B signaling mechanisms during brain development.Nat Neurosci,2012,151645~1654.
10 Mcclelland AC,Shefflercollins SI,Kayser MS,et al.Ephrin-B1 and ephrin-B2 mediate Eph B-dependent presynaptic development via syntenin-1.Proc Natl Acad Sci USA,2009,10620487~20492.
11 Lim BK,Matsuda N,Poo MM.Ephrin-B reverse signaling promotes structural and functional synaptic maturation in vivo.Nat Neurosci,2008,11160~169.
12 Vetere G,Restivo L,Cole CJ,et al.Spine growth in the anterior cingulate cortex is necessary for consolidation of contextual fear memory.Proc Natl Acad Sci USA,2011,1088456~8460.
13 Fu M,Yu X,Lu J,et al.Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo.Nature,2012,48392~95.
14 Zhu XN,Liu XD,Zhuang H,et al.Amygdala Eph B2 signaling regulates glutamatergic neuron maturation and innate fear.J Neurosci 2016,3610151~10162.
15 Chang CJ,Chang MY,Chou SY,et al.Ephexin1 is required for Eph-mediated limb trajectory of spinal motor axons.J Neurosci,2018,382043~2056.
16 Heintz TG,Eva R,Fawcett JW.Regional regulation of purkinje cell dendritic spines by integrins and Eph/Ephrins.PLos One,2016,11e0158558.
17 Das G,Yu Q,Hui R,et al.Eph A5 and Eph A6:regulation of neuronal and spine morphology.Cell Biosci,2016,648.
18 Clifford MA,Athar W,Leonard CE,et al.Eph A7 signaling guides cortical dendritic development and spine maturation.Proc Natl Acad Sci USA,2014,1114994~4999.
19 Xu NJ,Sun S,Gibson JR,et al.A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses.Nat Neurosci,2011,141421~1429.
20 Contractor A,Heinemann SF.Trans-synaptic Eph receptorephrin signaling in hippocampal mossy fiber LTP.Science,2002,2961864~1869.
21 Filosa A,Paixao S,Honsek SD,et al.Neuron-glia communication via Eph A4/ephrin-A3 modulates LTP through glial glutamate transport.Nat Neurosci,2009,121285~1292.
22 Chen BS,Roche KW.Regulation of NMDA receptors by phosphorylation.Neuropharmacology,2007,53362~368.
23 Nolt MJ,Lin Y,Hruska M,et al.Eph B controls NMDAreceptor function and synaptic targeting in a subunit-specific manner.J Neurosci,2011,315353~5364.
24 Antion MD,Christie LA,Bond AM,et al.Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses.Mol Cell Neurosci,2010,45378~388.
25 Semerdjieva S,Abdulrazak HH,Salim SS,et al.Activation of Eph A receptors mediates the recruitment of the adaptor protein Slap,contributing to the downregulation of N-methyl-D-aspartate receptors.Mol Cell Biol,2013,331442~1455.
26 Taylor H,Campbell J,Nobes CD.Ephs and ephrins.Curr Biol,2017,27R90~R95.
27 Shi XD,Sun K,Hu R,et al.Blocking the interaction between Eph B2 and ADDLs by a small peptide rescues impaired synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease.J Neurosci,2016,3611959~11973.
28 PlanagumàJ,Haselmann H,Mannara F,et al.Ephrin-B2prevents N-methyl-D-aspartate receptor antibody effects on memory and neuroplasticity.Ann Neurol,2016,80388~400.
2 Hruska M,Dalva MB.Ephrin regulation of synapse formation,function and plasticity.Mol Cell Neurosci,2012,5035~44.
3 Kania A,Klein R.Mechanisms of ephrin-Eph signalling in development,physiology and disease.Nat Rev Mol Cell Biol,2016,17240~256.
4 Monica D,Raphael L.The role of Ephs and ephrins in memory formation.Int J Neuropsychopharmacol,2016,19pyv106.
5 Dines M,Grinberg S,Vassiliev M,et al.The roles of Eph receptors in contextual fear conditioning memory formation.Neurobiol Learn Mem,2015,12462~70.
6 Alapin JM,Dines M,Vassiliev M,et al.Activation of Eph B2 forward signaling enhances memory consolidation.Cell Rep,2018,232014~2025.
7 Dines M,Lamprecht R.Ephrin A4 mimetic peptide targeted to Eph A binding site impairs the formation of long-term fear memory in lateral amygdala.Transl Psychiatry,2014,4e450.
8 Srivastava N,Robichaux MA,Chenaux G,et al.Eph B2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak.Mol Cell Neurosci,2013,52106~116.
9 Soskis MJ,Ho HY,Bloodgood BL,et al.A chemical genetic approach reveals distinct Eph B signaling mechanisms during brain development.Nat Neurosci,2012,151645~1654.
10 Mcclelland AC,Shefflercollins SI,Kayser MS,et al.Ephrin-B1 and ephrin-B2 mediate Eph B-dependent presynaptic development via syntenin-1.Proc Natl Acad Sci USA,2009,10620487~20492.
11 Lim BK,Matsuda N,Poo MM.Ephrin-B reverse signaling promotes structural and functional synaptic maturation in vivo.Nat Neurosci,2008,11160~169.
12 Vetere G,Restivo L,Cole CJ,et al.Spine growth in the anterior cingulate cortex is necessary for consolidation of contextual fear memory.Proc Natl Acad Sci USA,2011,1088456~8460.
13 Fu M,Yu X,Lu J,et al.Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo.Nature,2012,48392~95.
14 Zhu XN,Liu XD,Zhuang H,et al.Amygdala Eph B2 signaling regulates glutamatergic neuron maturation and innate fear.J Neurosci 2016,3610151~10162.
15 Chang CJ,Chang MY,Chou SY,et al.Ephexin1 is required for Eph-mediated limb trajectory of spinal motor axons.J Neurosci,2018,382043~2056.
16 Heintz TG,Eva R,Fawcett JW.Regional regulation of purkinje cell dendritic spines by integrins and Eph/Ephrins.PLos One,2016,11e0158558.
17 Das G,Yu Q,Hui R,et al.Eph A5 and Eph A6:regulation of neuronal and spine morphology.Cell Biosci,2016,648.
18 Clifford MA,Athar W,Leonard CE,et al.Eph A7 signaling guides cortical dendritic development and spine maturation.Proc Natl Acad Sci USA,2014,1114994~4999.
19 Xu NJ,Sun S,Gibson JR,et al.A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses.Nat Neurosci,2011,141421~1429.
20 Contractor A,Heinemann SF.Trans-synaptic Eph receptorephrin signaling in hippocampal mossy fiber LTP.Science,2002,2961864~1869.
21 Filosa A,Paixao S,Honsek SD,et al.Neuron-glia communication via Eph A4/ephrin-A3 modulates LTP through glial glutamate transport.Nat Neurosci,2009,121285~1292.
22 Chen BS,Roche KW.Regulation of NMDA receptors by phosphorylation.Neuropharmacology,2007,53362~368.
23 Nolt MJ,Lin Y,Hruska M,et al.Eph B controls NMDAreceptor function and synaptic targeting in a subunit-specific manner.J Neurosci,2011,315353~5364.
24 Antion MD,Christie LA,Bond AM,et al.Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses.Mol Cell Neurosci,2010,45378~388.
25 Semerdjieva S,Abdulrazak HH,Salim SS,et al.Activation of Eph A receptors mediates the recruitment of the adaptor protein Slap,contributing to the downregulation of N-methyl-D-aspartate receptors.Mol Cell Biol,2013,331442~1455.
26 Taylor H,Campbell J,Nobes CD.Ephs and ephrins.Curr Biol,2017,27R90~R95.
27 Shi XD,Sun K,Hu R,et al.Blocking the interaction between Eph B2 and ADDLs by a small peptide rescues impaired synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease.J Neurosci,2016,3611959~11973.
28 PlanagumàJ,Haselmann H,Mannara F,et al.Ephrin-B2prevents N-methyl-D-aspartate receptor antibody effects on memory and neuroplasticity.Ann Neurol,2016,80388~400.