Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner

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Item Type:	Article
Title:	Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner
Creators Name:	DiBattista, A.M., Dumanis, S.B., Song, J.M., Bu, G., Weeber, E., Rebeck, G.W. and Hoe, H.S.
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 CaMKIIalpha or CaMKIIbeta. Taken together, our results suggest that VLDLR requires RasGRF1/CaMKII to alter dendritic spine formation.
Keywords:	VLDLR, Dendritic Spine, Ras, CaMKII, Alzheimer's Disease, ApoE Receptor, Animals, Mice, Rats
Source:	Biochimica et Biophysica Acta - Molecular Cell Research
ISSN:	0167-4889
Publisher:	Elsevier
Volume:	1853
Number:	5
Page Range:	904-917
Date:	May 2015
Additional Information:	Copyright © 2015 Elsevier B.V. All rights reserved.
Official Publication:	https://doi.org/10.1016/j.bbamcr.2015.01.015
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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