School of Life Sciences, Nanchang University, Nanchang, Jiangxi, China.
School of Basic Medical Sciences, Nanchang University, Nanchang, China.
Mol Brain. 2020 Dec 10;13(1):166. doi: 10.1186/s13041-020-00708-z.
The low-density lipoprotein receptor-related protein 4 (LRP4) is essential for inducing the neuromuscular junction (NMJ) formation in muscle fibers, and LRP4 plays a critical role in dendritic development and synaptogenesis in the central nervous system (CNS). As a single transmembrane protein, LRP4 contains an enormously sizeable extracellular domain (ECD), containing multiple LDLα repeats in the N-terminal of ECD. LRP4 only with extracellular domain acts as a similar mechanism of full-length LRP4 in muscles to stimulate acetylcholine receptor clustering. In this study, we elucidated that LDLα repeats of LRP4 maintained the body weight and survival rate. Dendritic branches of the pyramidal neurons in Lrp4-null mice with LRP4 LDLα repeats residue were more than in Lrp4-null mice without residual LRP4 domain. Supplement with conditioned medium from LRP4 LDLα overexpression cells, the primary culture pyramidal neurons achieved strong dendritic arborization ability. Besides, astrocytes with LRP4 LDLα repeats residue could promote pyramidal neuronal dendrite arborization in the primary co-cultured system. These observations signify that LRP4 LDLα repeats play a prominent underlying role in dendrite arborization.
低密度脂蛋白受体相关蛋白 4（LRP4）对于在肌肉纤维中诱导神经肌肉接头（NMJ）的形成是必需的，并且 LRP4 在中枢神经系统（CNS）中的树突发育和突触发生中起着关键作用。作为一种单一的跨膜蛋白，LRP4 含有一个非常大的细胞外结构域（ECD），其 ECD 的 N 端含有多个 LDLα 重复序列。LRP4 仅具有细胞外结构域，在肌肉中以类似于全长 LRP4 的机制刺激乙酰胆碱受体聚集。在这项研究中，我们阐明了 LRP4 的 LDLα 重复序列维持了体重和存活率。LRP4 缺失小鼠的 LRP4 LDLα 重复序列残基的锥体神经元树突分支比没有 LRP4 残留结构域的 LRP4 缺失小鼠多。补充 LRP4 LDLα 过表达细胞的条件培养基后，原代培养的锥体神经元具有很强的树突分支能力。此外，具有 LRP4 LDLα 重复序列残基的星形胶质细胞可以促进原代共培养系统中锥体神经元树突的分支。这些观察结果表明 LRP4 LDLα 重复序列在树突分支中起着突出的作用。
