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ApoE receptor 2 regulates synapse and dendritic spine formation.

BACKGROUND: Apolipoprotein E receptor 2 (ApoEr2) is a postsynaptic protein involved in long-term potentiation (LTP), learning, and memory through unknown mechanisms. We examined the biological effects of ApoEr2 on synapse and dendritic spine formation-processes critical for learning and memory. METHODOLOGY/PRINCIPAL FINDINGS: In a heterologous co-culture synapse assay, overexpression of ApoEr2 in COS7 cells significantly increased colocalization with synaptophysin in primary hippocampal neurons, suggesting that ApoEr2 promotes interaction with presynaptic structures. In primary neuronal cultures, overexpression of ApoEr2 increased dendritic spine density. Consistent with our in vitro findings, ApoEr2 knockout mice had decreased dendritic spine density in cortical layers II/III at 1 month of age. We also tested whether the interaction between ApoEr2 and its cytoplasmic adaptor proteins, specifically X11α and PSD-95, affected synapse and dendritic spine formation. X11α decreased cell surface levels of ApoEr2 along with synapse and dendritic spine density. In contrast, PSD-95 increased cell surface levels of ApoEr2 as well as synapse and dendritic spine density. CONCLUSIONS/SIGNIFICANCE: These results suggest that ApoEr2 plays important roles in structure and function of CNS synapses and dendritic spines, and that these roles are modulated by cytoplasmic adaptor proteins X11α and PSD-95.

Pubmed ID: 21347244

Authors

  • Dumanis SB
  • Cha HJ
  • Song JM
  • Trotter JH
  • Spitzer M
  • Lee JY
  • Weeber EJ
  • Turner RS
  • Pak DT
  • Rebeck GW
  • Hoe HS

Journal

PloS one

Publication Data

February 24, 2011

Associated Grants

  • Agency: NIA NIH HHS, Id: AG026478
  • Agency: NIA NIH HHS, Id: AG032330
  • Agency: NIA NIH HHS, Id: AG032330-02S1
  • Agency: NIA NIH HHS, Id: AG034253
  • Agency: NINDS NIH HHS, Id: NS048085
  • Agency: NIA NIH HHS, Id: P01 AG030128
  • Agency: NIA NIH HHS, Id: P01 AG030128
  • Agency: NIA NIH HHS, Id: R01 AG026478
  • Agency: NINDS NIH HHS, Id: R01 NS048085
  • Agency: NINDS NIH HHS, Id: R01 NS048085-05
  • Agency: NIA NIH HHS, Id: R03 AG034253
  • Agency: NIA NIH HHS, Id: R03 AG034253-02

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • COS Cells
  • Cercopithecus aethiops
  • Coculture Techniques
  • Cytoplasm
  • Dendritic Spines
  • Extracellular Space
  • Guanylate Kinase
  • Hippocampus
  • Humans
  • LDL-Receptor Related Proteins
  • Membrane Proteins
  • Mice
  • Nerve Tissue Proteins
  • Protein Structure, Tertiary
  • Receptors, AMPA
  • Synapses