Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix
Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix
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DOI：
10.1073/pnas.96.14.7932
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Goldgaber, D
中科院分区：
文献类型：
--
作者：
Schwarzman, AL;Singh, N;Goldgaber, D
大多数家族性早发性阿尔茨海默病病例是由早老素1 （PS1）基因突变引起的。内源性PS1的亚细胞定位对于了解其功能、与蛋白质的相互作用以及在阿尔茨海默病中的作用至关重要。尽管许多研究表明，PS1主要定位于内质网和高尔基体，但关于PS1定位于细胞表面的报道存在矛盾。我们发现内源性PS1在T淋巴细胞（Jurkat细胞）中高度表达。使用多种方法，我们提出的证据表明，内源性PSI定位于细胞表面，除了细胞膜间室。此外，当细胞与胶原基质黏附时，PS1在板足表面出现高水平表达。细胞表面-PS1与肌动蛋白结合蛋白丝蛋白（ABP-280）在体内形成复合物，已知其在细胞表面受体和细胞骨架之间形成桥梁，介导细胞粘附和细胞运动。综上所述，我们的结果表明PSI在细胞粘附和/或细胞-基质相互作用中的作用。
Most familial early-onset Alzheimer's disease cases are caused by mutations in the presenilin 1 (PS1) gene. Subcellular localization of the endogenous PS1 is essential for understanding its function, interactions with proteins, and role in Alzheimer's disease, Although numerous studies revealed predominant localization of PSI to endoplasmic reticulum and Golgi, there are conflicting reports on the localization of PS1 to the cell surface. We found that endogenous PS1 is highly expressed in T lymphocytes (Jurkat cells). Using a variety of methods, we present evidence that endogenous PSI is localized to the cell surface in addition to intracellular membrane compartments. Moreover, PS1 appeared in high levels on the surface of lamellipodia upon adhesion of the cells to a collagen matrix. The redistribution of PS1 in adhered cells was strikingly similar to that of the well characterized adhesion protein CD44, Cell surface-PS1 formed complexes in vivo with actin-binding protein filamin (ABP-280), which is known to form bridges between cell surface receptors and cytoskeleton and mediate cell adhesion and cell motility. Taken together, our results suggest a role of PSI in cell adhesion and/or cell-matrix interaction.