title: ApoE receptor 2 regulates synapse and dendritic spine formation.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Sonya B
authors.initials: SB
authors.lastname: Dumanis
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Cha
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Song
authors.forename: Justin H
authors.initials: JH
authors.lastname: Trotter
authors.forename: Matthew
authors.initials: M
authors.lastname: Spitzer
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
authors.forename: R Scott
authors.initials: RS
authors.lastname: Turner
authors.forename: Daniel T S
authors.initials: DT
authors.lastname: Pak
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Hoe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D003593:Cytoplasm / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D005110:Extracellular Space / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513072:Apba1 protein, mouse; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D026502:LDL-Receptor Related Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C098773:low density lipoprotein receptor-related protein 8; D051528:Guanylate Kinases