ApoE Receptor 2 Regulates Synapse and Dendritic Spine Formation

作者：Dumanis Sonya B^*; Cha Hyun Jung; Song Jung Min; Trotter Justin H; Spitzer Matthew; Lee Ji Yun; Weeber Edwin J; Turner R Scott; Pak Daniel T S; Rebeck G William; Hoe Hyang Sook

来源：PLos One, 2011, 6(2): e17203.

DOI：10.1371/journal.pone.0017203

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 X11 alpha and PSD-95, affected synapse and dendritic spine formation. X11 alpha 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 X11 alpha and PSD-95.

• 出版日期2011-2-15