title: Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner.
abstract: Very Low Density Lipoprotein Receptor (VLDLR) is an apolipoprotein E receptor involved in synaptic plasticity, learning, and memory. However, it is unknown how VLDLR can regulate synaptic and cognitive function. In the present study, we found that VLDLR is present at the synapse both pre- and post-synaptically. Overexpression of VLDLR significantly increases, while knockdown of VLDLR decreases, dendritic spine number in primary hippocampal cultures. Additionally, knockdown of VLDLR significantly decreases synaptophysin puncta number while differentially regulating cell surface and total levels of glutamate receptor subunits. To identify the mechanism by which VLDLR induces these synaptic effects, we investigated whether VLDLR affects dendritic spine formation through the Ras signaling pathway, which is involved in spinogenesis and neurodegeneration. Interestingly, we found that VLDLR interacts with RasGRF1, a Ras effector, and knockdown of RasGRF1 blocks the effect of VLDLR on spinogenesis. Moreover, we found that VLDLR did not rescue the deficits induced by the absence of Ras signaling proteins CaMKIIα or CaMKIIβ. Taken together, our results suggest that VLDLR requires RasGRF1/CaMKII to alter dendritic spine formation.
authors: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Amanda Marie
authors: AM
authors: DiBattista
authors: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Max Delbreuck Center for Molecular Medicine, Berlin, Germany.
authors: Sonya B
authors: SB
authors: Dumanis
authors: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Jung Min
authors: JM
authors: Song
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
authors: Guojun
authors: G
authors: Bu
authors: Department of Molecular Pharmacology and Physiology, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.
authors: Edwin
authors: E
authors: Weeber
authors: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: G William
authors: GW
authors: Rebeck
authors: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: sookhoe72@kbri.re.kr.
authors: Hyang-Sook
authors: HS
authors: Hoe
mesh_terms: D000818:Animals; D019556:COS Cells; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D020666:ras-GRF1 / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; C121673:Gprin1 protein, mouse; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D016194:Receptors, N-Methyl-D-Aspartate; D000091042:Reelin Protein; D016708:Synaptophysin; C036053:VLDL receptor; D020666:ras-GRF1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D012697:Serine Endopeptidases
keywords: Alzheimer's disease; ApoE receptor; CaMKII; Dendritic spine; Ras; VLDLR
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