Lrp4 Ldl Alpha Repeats Of Astrocyte Enhance Dendrite Arborization Of The Neuron

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 LDL alpha 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 LDL alpha repeats of LRP4 maintained the body weight and survival rate. Dendritic branches of the pyramidal neurons in Lrp4-null mice with LRP4 LDL alpha repeats residue were more than in Lrp4-null mice without residual LRP4 domain. Supplement with conditioned medium from LRP4 LDL alpha overexpression cells, the primary culture pyramidal neurons achieved strong dendritic arborization ability. Besides, astrocytes with LRP4 LDL alpha repeats residue could promote pyramidal neuronal dendrite arborization in the primary co-cultured system. These observations signify that LRP4 LDL alpha repeats play a prominent underlying role in dendrite arborization.