PAT1在小鼠原代神经元中反向调节淀粉样前体蛋白的表面水平。
PAT1 inversely regulates the surface Amyloid Precursor Protein level in mouse primary neurons.
作者信息
Dilsizoglu Senol Aysegul, Tagliafierro Lidia, Huguet Léa, Gorisse-Hussonnois Lucie, Chasseigneaux Stéphanie, Allinquant Bernadette
机构信息
INSERM UMR 894, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy.
出版信息
BMC Neurosci. 2015 Mar 7;16:10. doi: 10.1186/s12868-015-0152-8.
BACKGROUND
The amyloid precursor protein (APP) is a key molecule in Alzheimer disease. Its localization at the cell surface can trigger downstream signaling and APP cleavages. APP trafficking to the cell surface in neurons is not clearly understood and may be related to the interactions with its partners. In this respect, by having homologies with kinesin light chain domains and because of its capacity to bind APP, PAT1 represents a good candidate.
RESULTS
We observed that PAT1 binds poorly APP at the cell surface of primary cortical neurons contrary to cytoplasmic APP. Using down and up-regulation of PAT1, we observed respectively an increase and decrease of APP at the cell surface. The increase of APP at the cell surface induced by low levels of PAT1 did not trigger cell death signaling.
CONCLUSIONS
These data suggest that PAT1 slows down APP trafficking to the cell surface in primary cortical neurons. Our results contribute to the elucidation of mechanisms involved in APP trafficking in Alzheimer disease.
背景
淀粉样前体蛋白（APP）是阿尔茨海默病中的关键分子。其在细胞表面的定位可触发下游信号传导和APP的切割。神经元中APP转运至细胞表面的机制尚不清楚，可能与其与伙伴分子的相互作用有关。在这方面，PAT1由于与驱动蛋白轻链结构域具有同源性且有结合APP的能力，是一个很好的候选分子。
结果
我们观察到，与细胞质中的APP相反，PAT1在原代皮质神经元细胞表面与APP的结合较差。通过下调和上调PAT1，我们分别观察到细胞表面APP的增加和减少。低水平PAT1诱导的细胞表面APP增加并未触发细胞死亡信号。
结论
这些数据表明，PAT1减缓了原代皮质神经元中APP向细胞表面的转运。我们的结果有助于阐明阿尔茨海默病中APP转运所涉及的机制。
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