LRP-1 and LRP-2 receptors function in the membrane neuron. Trafficking mechanisms and proteolytic processing in Alzheimer's disease.
LRP-1 and LRP-2 receptors function in the membrane neuron. Trafficking mechanisms and proteolytic processing in Alzheimer's disease.
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DOI：
10.3389/fphys.2012.00269
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发表时间：
2012
影响因子：
4
通讯作者：
Navarro C
中科院分区：
文献类型：
--
作者：
Spuch C;Ortolano S;Navarro C
低密度脂蛋白受体相关蛋白（LRP）属于低密度脂蛋白受体家族，通常被认为是细胞表面内吞受体，其结合并内化细胞外配体在溶酶体中降解。神经元需要胆固醇才能发挥作用并保持膜筏稳定。神经元中的胆固醇摄取是由 ApoE 通过细胞表面的 LRP 受体进行的。在神经元中，最重要的是 LRP-1 和 LRP-2，甚至人们认为阿尔茨海默病 (AD) 的致病因素是该过程的故障，导致细胞内信号传导以及营养物质和有毒化合物的储存和/或释放受损。这两种受体都是多功能细胞表面受体，广泛表达于包括神经元和星形胶质细胞在内的多种组织中。 LRP 由细胞内 (ICD) 和细胞外结构域 (ECD) 构成。通过其 ECD，LRP 结合至少 40 种不同的配体，从脂蛋白和蛋白酶抑制剂复合物到生长因子和细胞外基质蛋白。这些受体还被证明可以通过其 ICD 以磷酸化依赖性方式与支架和信号蛋白相互作用，并作为与其他细胞表面或整合膜蛋白合作的共受体发挥作用。因此，LRP 涉及两个主要的生理过程：内吞作用和信号通路的调节，这两者都涉及多种生物学作用，包括脂质代谢、细胞生长过程、蛋白酶降解和组织侵袭。有趣的是，LRP 也定位于不同阶段的神经元中，这表明这两种受体可能与胚胎发育、神经元生长或 AD 发病机制中的信号转导有关。
Low density lipoprotein receptor-related protein (LRP) belongs to the low-density lipoprotein receptor family, generally recognized as cell surface endocytic receptors, which bind and internalize extracellular ligands for degradation in lysosomes. Neurons require cholesterol to function and keep the membrane rafts stable. Cholesterol uptake into the neuron is carried out by ApoE via LRPs receptors on the cell surface. In neurons the most important are LRP-1 and LRP-2, even it is thought that a causal factor in Alzheimer's disease (AD) is the malfunction of this process which cause impairment intracellular signaling as well as storage and/or release of nutrients and toxic compounds. Both receptors are multifunctional cell surface receptors that are widely expressed in several tissues including neurons and astrocytes. LRPs are constituted by an intracellular (ICD) and extracellular domain (ECD). Through its ECD, LRPs bind at least 40 different ligands ranging from lipoprotein and protease inhibitor complex to growth factors and extracellular matrix proteins. These receptors has also been shown to interact with scaffolding and signaling proteins via its ICD in a phosphorylation-dependent manner and to function as a co-receptor partnering with other cell surface or integral membrane proteins. Thus, LRPs are implicated in two major physiological processes: endocytosis and regulation of signaling pathways, which are both involved in diverse biological roles including lipid metabolism, cell growth processes, degradation of proteases, and tissue invasion. Interestingly, LRPs were also localized in neurons in different stages, suggesting that both receptors could be implicated in signal transduction during embryonic development, neuronal outgrowth or in the pathogenesis of AD.
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影响因子：
4.7
作者：
Bento-Abreu, Andre;Velasco, Ana;Medina, Jose M.
通讯作者：
Medina, Jose M.
影响因子：
13.6
作者：
Birn, H;Vorum, H;Christensen, EI
通讯作者：
Christensen, EI
影响因子：
4.7
作者：
BRUNDEN, KR;RICHTERCOOK, NJ;FREDERICKSON, RCA
通讯作者：
FREDERICKSON, RCA
DOI：
10.1159/000134088
发表时间：
1995-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
CHOWDHARY, BP;LUNDGREN, S;RASK, L
通讯作者：
RASK, L
DOI：
10.1006/bbrc.2000.2441
发表时间：
2000-04-13
影响因子：
3.1
作者：
Chan, WL;Shaw, PC;Nielsen, MS
通讯作者：
Nielsen, MS