A role for LRP4 in neuronal cell viability is related to apoE-binding.
The distribution pattern of apolipoprotein E (apoE) in cortical neurons in culture resembles that of low-density lipoprotein receptor-related protein 4 (LRP4). Both proteins are distributed in a punctate manner on the cell surface throughout neurons, including somas and dendrites. This finding prompted us to examine whether apoE is a ligand for LRP4 in the rat brain. ApoE and LRP4 from both Cos7 cells heterologous expressing LRP4 and brain homogenate were co-immunoprecipitated. We then examined the effect of antibody against the ligand-binding domain of LRP4 (anti-LB). Anti-LB applied to neuronal cells in culture down-regulated MAP2-immunoreactive neurons, reduced the viability of neurons and impaired synaptic structure. This effect was possibly due to a blockade of the binding of extraneuronal ligands, such as apoE/cholesterol, to LRP4 protein, since anti-LB suppressed binding of apoE to the LRP4 heterologously expressed in Cos7 cells. These results suggest that apoE is an endogenous ligand for LRP4 and may play a role as a receptor for extracellular signals, including those from glial cells, in the maintenance of the viability of neurons.
Lu
Yonghao
Y
Department of Neuroplasticity, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Tian
Qing Bao
QB
Endo
Shogo
S
Suzuki
Tatsuo
T
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D019556:COS Cells; D002470:Cell Survival / Q000502:physiology; D002499:Centrifugation, Density Gradient; D002522:Chlorocebus aethiops; D003080:Cold Temperature; D003902:Detergents; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008024:Ligands; D021962:Membrane Microdomains / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D017830:Octoxynol; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure; D014162:Transfection
D001057:Apolipoproteins E; D003902:Detergents; D008024:Ligands; C525701:Lrp4 protein, rat; D011973:Receptors, LDL; D017830:Octoxynol