APP Protein Family Signaling at the Synapse: Insights from Intracellular APP-Binding Proteins.
APP Protein Family Signaling at the Synapse: Insights from Intracellular APP-Binding Proteins.
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DOI：
10.3389/fnmol.2017.00087
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发表时间：
2017
影响因子：
4.8
通讯作者：
Kins S
中科院分区：
文献类型：
--
作者：
Guénette S;Strecker P;Kins S
了解淀粉样蛋白前体蛋白家族（APP/APP样蛋白，APLP）在神经系统中功能的分子机制可以通过研究APP/APLP相互作用组来实现。在这篇综述文章中，我们聚焦于结合位于c端区域最后15个氨基酸的ynpty内化基序的细胞内APP相互作用蛋白。这些蛋白包括X11/ munc -18相互作用蛋白（Mints）和FE65/ fe65l，代表APP胞浆结合伙伴，表现出不同的神经元功能。通过对FE65和APP家族成员突变小鼠的比较，我们发现APP/FE65蛋白家族成员在神经发生和神经元定位中具有共同的功能。越来越多的证据也支持膜相关APP/APLP蛋白在突触形成和功能中的作用。因此，我们很容易推测APP/APLP c端相互作用蛋白在突触传递APP/APLP依赖性信号。在此，我们比较了目前对APP/APLP突变小鼠与缺乏不同APP/APLP相互作用伙伴小鼠突触表型的了解，并讨论了APP依赖的FE65/FE65L或X11/Mint信号可能对突触囊泡释放、突触形态和功能的下游影响。鉴于X11/Mint蛋白在突触中的作用已经确立，我们提出了一个强调FE65蛋白家族成员在突触中APP/APLP生理功能转导作用的模型。
Understanding the molecular mechanisms underlying amyloid precursor protein family (APP/APP-like proteins, APLP) function in the nervous system can be achieved by studying the APP/APLP interactome. In this review article, we focused on intracellular APP interacting proteins that bind the YENPTY internalization motif located in the last 15 amino acids of the C-terminal region. These proteins, which include X11/Munc-18-interacting proteins (Mints) and FE65/FE65Ls, represent APP cytosolic binding partners exhibiting different neuronal functions. A comparison of FE65 and APP family member mutant mice revealed a shared function for APP/FE65 protein family members in neurogenesis and neuronal positioning. Accumulating evidence also supports a role for membrane-associated APP/APLP proteins in synapse formation and function. Therefore, it is tempting to speculate that APP/APLP C-terminal interacting proteins transmit APP/APLP-dependent signals at the synapse. Herein, we compare our current knowledge of the synaptic phenotypes of APP/APLP mutant mice with those of mice lacking different APP/APLP interaction partners and discuss the possible downstream effects of APP-dependent FE65/FE65L or X11/Mint signaling on synaptic vesicle release, synaptic morphology and function. Given that the role of X11/Mint proteins at the synapse is well-established, we propose a model highlighting the role of FE65 protein family members for transduction of APP/APLP physiological function at the synapse.