Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Mol Cell Neurosci. 2010 Apr;43(4):341-52. doi: 10.1016/j.mcn.2010.01.001. Epub 2010 Jan 18.
AMPA receptor binding protein (ABP) is a multi-PDZ domain scaffold that binds and stabilizes AMPA receptor (AMPAR) GluR2/3 subunits at synapses. A palmitoylated N-terminal splice variant (pABP-L) concentrates in spine heads, whereas a non-palmitoylated form (ABP-L) is intracellular. We show that postsynaptic Sindbis viral expression of pABP-L increased AMPAR mediated mEPSC amplitude and frequency and elevated surface levels of GluR1 and GluR2, suggesting an increase in AMPA receptors at individual synapses. Spines were enlarged and more numerous and nerve terminals contacting these cells displayed enlarged synaptophysin puncta. A non-palmitoylated pABP-L mutant (C11A) did not change spine density or size. Exogenous pABP-L and endogenous GRIP, a related scaffold, colocalized with NPRAP (delta-catenin), to which ABP and GRIP bind, and with cadherins, which bind NPRAP. Thus postsynaptic pABP-L induces pre and postsynaptic changes that are dependent on palmitoylation and likely achieved through ABP association with a multi-molecular cell surface signaling complex.
AMPA 受体结合蛋白 (ABP) 是一种多 PDZ 结构域支架，可在突触处结合并稳定 AMPA 受体 (AMPAR) GluR2/3 亚基。一个棕榈酰化的 N 端剪接变体 (pABP-L) 集中在棘突头部，而非棕榈酰化形式 (ABP-L) 在细胞内。我们发现突触后辛德毕斯病毒表达的 pABP-L 增加了 AMPAR 介导的 mEPSC 幅度和频率，并提高了 GluR1 和 GluR2 的表面水平，表明单个突触处 AMPA 受体增加。棘突增大且数量增多，接触这些细胞的神经末梢显示出增大的突触小泡蛋白斑。非棕榈酰化的 pABP-L 突变体 (C11A) 不会改变棘突密度或大小。外源性 pABP-L 和内源性 GRIP（一种相关支架）与 NPRAP（delta-catenin）共定位，ABP 和 GRIP 与之结合，与钙黏蛋白共定位，钙黏蛋白与 NPRAP 结合。因此，突触后 pABP-L 诱导了前突触和后突触的变化，这依赖于棕榈酰化，并且可能通过 ABP 与多分子细胞表面信号复合物的结合来实现。
