The cross-talk of LDL-cholesterol with cell motility: Insights from the Niemann Pick Type C1 mutation and altered integrin trafficking
The cross-talk of LDL-cholesterol with cell motility: Insights from the Niemann Pick Type C1 mutation and altered integrin trafficking
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DOI：
10.1080/19336918.2015.1019996
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发表时间：
2015-09-01
影响因子：
3.2
通讯作者：
Grewal, Thomas
中科院分区：
文献类型：
--
作者：
Hoque, Monira;Rentero, Carles;Grewal, Thomas
胆固醇被认为是不可或缺的募集和功能的整合素在局灶性粘连细胞迁移。然而，控制整合素运输和粘着斑组装的生理胆固醇池仍不清楚。使用尼曼匹克C1型（NPC）突变细胞，其在晚期内体（LE）中积累低密度脂蛋白（LDL）衍生的胆固醇，最近的几项研究表明LDL-胆固醇在调节粘着斑动力学中具有多种作用。首先，从LE到粘着斑的内吞LDL-胆固醇的靶向控制它们在迁移细胞的前沿的形成。其他新出现的文献表明，这可能与整合素、Src激酶和金属蛋白酶从LE隔室到局灶性粘连的囊泡转运有关。其次，我们最近的工作确定LDL-胆固醇是决定几种可溶性NSF附着蛋白（SNAP）受体（SNARE）蛋白（囊泡转运中的关键参与者）的分布和能力的关键因素，以控制整合素转运至细胞表面和细胞外基质（ECM）分泌。总的来说，胆固醇代谢的饮食、遗传和病理变化可能与转移性癌细胞中整合素和ECM细胞表面递送的效率和速度有关。这篇评论将总结如何直接和间接途径使低密度脂蛋白胆固醇调节细胞运动。
Cholesterol is considered indispensible for the recruitment and functioning of integrins in focal adhesions for cell migration. However, the physiological cholesterol pools that control integrin trafficking and focal adhesion assembly remain unclear. Using Niemann Pick Type C1 (NPC) mutant cells, which accumulate Low Density lipoprotein (LDL)-derived cholesterol in late endosomes (LE), several recent studies indicate that LDL-cholesterol has multiple roles in regulating focal adhesion dynamics. Firstly, targeting of endocytosed LDL-cholesterol from LE to focal adhesions controls their formation at the leading edge of migrating cells. Other newly emerging literature suggests that this may be coupled to vesicular transport of integrins, Src kinase and metalloproteases from the LE compartment to focal adhesions. Secondly, our recent work identified LDL-cholesterol as a key factor that determines the distribution and ability of several Soluble NSF Attachment Protein (SNAP) Receptor (SNARE) proteins, key players in vesicle transport, to control integrin trafficking to the cell surface and extracellular matrix (ECM) secretion. Collectively, dietary, genetic and pathological changes in cholesterol metabolism may link with efficiency and speed of integrin and ECM cell surface delivery in metastatic cancer cells. This commentary will summarize how direct and indirect pathways enable LDL-cholesterol to modulate cell motility.