Migani Paolo, Bartlett Carole, Dunlop Sarah, Beazley Lyn, Rodger Jennifer
Istituto di Biochimica, Università Politecnica delle Marche, via Ranieri 66, 60131 Ancona, Italy.
Brain Res. 2009 Jan 9;1247:50-61. doi: 10.1016/j.brainres.2008.09.100. Epub 2008 Oct 17.
The membrane-bound proteins ephrins and their receptors, Eph receptor tyrosine kinases, are known for their key role during development of the central nervous system (CNS). Ligand/receptor interactions as a result of cell-cell contacts activate intracellular signalling pathways which mediate specific cellular responses. Activation can occur bidirectionally in both the receptor and the ligand-bearing cells. Eph receptor and ephrin families have been implicated in synaptic plasticity in the mature brain: effects include long-term potentiation/depression of excitatory transmission (LTP/LTD) and an action on the structure and number of synaptic contacts. However, due to the redundancy of binding between receptors and ligands, the role of individual proteins has not yet been completely elucidated. Ephrin-B1 has been suggested to play a role in synaptic plasticity in the hippocampus, but its expression and localization at pre- or post-synaptic sites has been poorly documented, most likely due to the apparent low activity of the corresponding gene in mature brain. Here we present immunohistochemical data demonstrating a broad but highly regulated cellular distribution of ephrin-B1 in the mature mouse brain. We show that ephrin-B1 is expressed post-synaptically on dendritic spines in the cortex, supporting a role in synaptic plasticity in this region. However, the prevalent extra-synaptic distribution in regions such as the hippocampus and cerebellum suggests an additional structural role, perhaps at the neuron/glia interface.
膜结合蛋白 Ephrins 及其受体 Eph 受体酪氨酸激酶,因其在中枢神经系统(CNS)发育过程中的关键作用而闻名。细胞间接触导致的配体/受体相互作用激活细胞内信号通路,介导特定的细胞反应。激活可在受体细胞和携带配体的细胞中双向发生。Eph 受体和 Ephrin 家族与成熟大脑中的突触可塑性有关:其作用包括兴奋性传递的长时程增强/抑制(LTP/LTD)以及对突触接触的结构和数量的影响。然而,由于受体和配体之间结合的冗余性,单个蛋白的作用尚未完全阐明。有人提出 Ephrin-B1 在海马体的突触可塑性中起作用,但其在突触前或突触后位点的表达和定位记录甚少,这很可能是由于相应基因在成熟大脑中明显低活性所致。在此,我们展示免疫组化数据,证明 Ephrin-B1 在成熟小鼠大脑中具有广泛但高度受调控的细胞分布。我们表明,Ephrin-B1 在皮质的树突棘上突触后表达,支持其在该区域突触可塑性中的作用。然而,在海马体和小脑等区域普遍存在的突触外分布表明其具有额外的结构作用,可能在神经元/胶质细胞界面。