Pohlkamp Theresa, Durakoglugil Murat, Lane-Donovan Courtney, Xian Xunde, Johnson Eric B, Hammer Robert E, Herz Joachim
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
PLoS One. 2015 Feb 17;10(2):e0116701. doi: 10.1371/journal.pone.0116701. eCollection 2015.
Apolipoprotein E (ApoE) genotype is the strongest predictor of Alzheimer's Disease (AD) risk. ApoE is a cholesterol transport protein that binds to members of the Low-Density Lipoprotein (LDL) Receptor family, which includes LDL Receptor Related Protein 4 (Lrp4). Lrp4, together with one of its ligands Agrin and its co-receptors Muscle Specific Kinase (MuSK) and Amyloid Precursor Protein (APP), regulates neuromuscular junction (NMJ) formation. All four proteins are also expressed in the adult brain, and APP, MuSK, and Agrin are required for normal synapse function in the CNS. Here, we show that Lrp4 is also required for normal hippocampal plasticity. In contrast to the closely related Lrp8/Apoer2, the intracellular domain of Lrp4 does not appear to be necessary for normal expression and maintenance of long-term potentiation at central synapses or for the formation and maintenance of peripheral NMJs. However, it does play a role in limb development.
载脂蛋白E（ApoE）基因型是阿尔茨海默病（AD）风险的最强预测指标。ApoE是一种胆固醇转运蛋白，可与低密度脂蛋白（LDL）受体家族的成员结合，该家族包括低密度脂蛋白受体相关蛋白4（Lrp4）。Lrp4与其配体之一聚集蛋白以及其共受体肌肉特异性激酶（MuSK）和淀粉样前体蛋白（APP）一起调节神经肌肉接头（NMJ）的形成。这四种蛋白质在成人大脑中也有表达，并且APP、MuSK和聚集蛋白是中枢神经系统正常突触功能所必需的。在这里，我们表明Lrp4也是正常海马可塑性所必需的。与密切相关的Lrp8/Apoer2不同，Lrp4的细胞内结构域对于中枢突触长期增强的正常表达和维持或外周神经肌肉接头的形成和维持似乎不是必需的。然而，它在肢体发育中确实发挥作用。
