title: Reciprocal regulation of very low density lipoprotein receptors (VLDLRs) in neurons by brain-derived neurotrophic factor (BDNF) and Reelin: involvement of the E3 ligase Mylip/Idol.
abstract: BDNF positively influences various aspects of neuronal migration, maturation, and survival in the developing brain. Reelin in turn mediates inhibitory signals to migrating neuroblasts, which is crucial for brain development. The interplay between BDNF and Reelin signaling in neurodevelopment is not fully understood. We show here that BDNF increased the levels of the Reelin receptor (VLDL receptor (VLDLR)) in hippocampal neurons by increasing gene expression. In contrast, Reelin decreased VLDLRs, which was accompanied by an increase in the levels of the E3 ligase Mylip/Idol in neurons. Down-regulation of Mylip/Idol using shRNAs abrogated the decrease in VLDLRs induced by Reelin. These results show that VLDLRs are tightly regulated in hippocampal neurons by both transcriptional and post-transcriptional mechanisms. The regulation of VLDLR by BDNF and Reelin may affect the migration of neurons and contribute to neurodevelopmental disorders in the nervous system.
authors.affiliation: From the Institute of Biomedicine/Biochemistry and Developmental Biology, University of Helsinki and.
authors.forename: Hai Thi
authors.initials: HT
authors.lastname: Do
authors.forename: Céline
authors.initials: C
authors.lastname: Bruelle
authors.forename: Timofey
authors.initials: T
authors.lastname: Tselykh
authors.forename: Pilvi
authors.initials: P
authors.lastname: Jalonen
authors.forename: Laura
authors.initials: L
authors.lastname: Korhonen
authors.forename: Dan
authors.initials: D
authors.lastname: Lindholm
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D015151:Immunoblotting; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D034622:RNA Interference; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C000717129:Reln protein, rat; C036053:VLDL receptor; C584833:Mylip protein, rat; D044767:Ubiquitin-Protein Ligases; D012697:Serine Endopeptidases
keywords: Brain-derived Neurotrophic Factor (BDNF); Neurodevelopment; Neurons; Receptor Regulation; Ubiquitin Ligase