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

Amanda Marie DiBattista, Sonya B. Dumanis, Jung Min Song, Guojun Bu, Edwin Weeber, G. William Rebeck, Hyang Sook Hoe

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)904-917
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number5
StatePublished - May 1 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier B.V.


  • Alzheimer's disease
  • ApoE receptor
  • CaMKII
  • Dendritic spine
  • Ras


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