Nakamura Y, Yamamoto M, Kumamaru E
Department of Pathology, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume, Japan.
Brain Res. 1998 May 18;793(1-2):47-53. doi: 10.1016/s0006-8993(98)00112-7.
The very low density lipoprotein receptor (VLDLR) was considered to specifically bind to VLDL rich apolipoprotein E (apoE). However, its distribution and functions in vivo have yet to be elucidated. In human and rat VLDLR, a variant form lacking 84 base pairs (bp) in O-linked sugar domain was noted but its significance was not initially understood. This study shows that the variant form of VLDLR coexists with full-length VLDLR in majority of tissues but is a major component in the white matter of human brain. The tissue distribution of a variant VLDLR was detected in myelin as well as in other tissues except for the liver with immunohistochemistry using a monoclonal antibody. This variant VLDLR is proposed to be functionally important for internalizing apoE in human brain. ApoE is associated with beta-amyloid in senile plaques and plays a role in the transport of the beta-amyloid. The presence of VLDLR in myelin may be one explanation as to why beta-amyloid does not accumulate in the white matter which is rich in VLDLR. Recently, evidences on VLDLR obtained mainly using knock-out or transfected mice suggest this receptor to be neither specific for VLDL nor functionally important in mammals. However, no variant form of VLDLR was found in any tissues of mouse. This variant form of VLDLR should thus be studied in greater detail using human tissues or cells.
极低密度脂蛋白受体（VLDLR）被认为能特异性结合富含载脂蛋白E（apoE）的极低密度脂蛋白。然而，其在体内的分布和功能尚未阐明。在人和大鼠的VLDLR中，发现了一种在O-连接糖结构域缺失84个碱基对（bp）的变异形式，但其意义最初并不清楚。本研究表明，VLDLR的变异形式与全长VLDLR在大多数组织中共存，但却是人脑白质中的主要成分。使用单克隆抗体通过免疫组织化学方法在髓磷脂以及除肝脏外的其他组织中检测到了变异型VLDLR的组织分布。有人提出这种变异型VLDLR在人脑内化apoE方面具有重要功能。ApoE与老年斑中的β-淀粉样蛋白相关，并在β-淀粉样蛋白的转运中起作用。髓磷脂中存在VLDLR可能是β-淀粉样蛋白在富含VLDLR的白质中不积累的一个原因。最近，主要使用基因敲除或转染小鼠获得的关于VLDLR的证据表明，该受体对极低密度脂蛋白既不具有特异性，在哺乳动物中也不具有重要功能。然而，在小鼠的任何组织中都未发现VLDLR的变异形式。因此，应该使用人体组织或细胞对这种变异型VLDLR进行更详细的研究。
