C-terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3
C-terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3
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DOI：
10.1111/j.1471-4159.2004.02910.x
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发表时间：
2005-02-01
影响因子：
4.7
通讯作者：
Gundelfinger, ED
中科院分区：
文献类型：
--
作者：
Boeckers, TM;Liedtke, T;Gundelfinger, ED
突触是一种特殊的接触点，负责调节神经元之间的交流。突触发生需要通过鲜为人知的机制在突触接触两侧特定地组装蛋白质簇。我们研究了被认为是突触后密度的主要支架分子的ProSAP/Shank家族多域蛋白的突触靶向性。与Shank1相反，绿色荧光蛋白(GFP)标记的ProSAP1/SHANK2和ProSAP2/Shank3缺失结构在海马神经元中的表达表明，它们的突触后定位依赖于C末端的完整性。最短的针对突触位点的构建包括ProSAP1/SHANK2的最后417个氨基酸，并包括C末端不育α基序(SAM)结构域。从该结构的N-末端去除54个残基导致在细胞质中的弥漫分布。总之，我们的数据描绘了ProSAP1/SHANK2和ProSAP2/Shank3中迄今未知的靶向信号，并为这些蛋白及其密切同源物Shank1在不同的分子途径中的含义提供了证据。
Synapses are specialized contact sites mediating communication between neurons. Synaptogenesis requires the specific assembly of protein clusters at both sides of the synaptic contact by mechanisms that are barely understood. We studied the synaptic targeting of multi-domain proteins of the ProSAP/Shank family thought to serve as master scaffolding molecules of the postsynaptic density. In contrast to Shank1, expression of green-fluorescent protein (GFP)-tagged ProSAP1/Shank2 and ProSAP2/Shank3 deletion constructs in hippocampal neurons revealed that their postsynaptic localization relies on the integrity of the C-termini. The shortest construct that was perfectly targeted to synaptic sites included the last 417 amino acids of ProSAP1/Shank2 and included the C-terminal sterile alpha motif (SAM) domain. Removal of 54 residues from the N-terminus of this construct resulted in a diffuse distribution in the cytoplasm. Altogether, our data delineate a hitherto unknown targeting signal in both ProSAP1/Shank2 and ProSAP2/Shank3 and provide evidence for an implication of these proteins and their close homologue, Shank1, in distinct molecular pathways.