The MIND-Center, Department of Medical Biochemistry, University of Aarhus, Ole Worms Allé 1170, DK 8000 Aarhus C, Denmark.
J Cell Sci. 2011 Apr 1;124(Pt 7):1095-105. doi: 10.1242/jcs.072538. Epub 2011 Mar 8.
Many different tissues and cell types exhibit regulated secretion of lipoprotein lipase (LPL). However, the sorting of LPL in the trans Golgi network has not, hitherto, been understood in detail. Here, we characterize the role of SorLA (officially known as SorLA-1 or sortilin-related receptor) in the intracellular trafficking of LPL. We found that LPL bound to SorLA under neutral and acidic conditions, and in cells this binding mainly occurred in vesicular structures. SorLA expression changed the subcellular distribution of LPL so it became more concentrated in endosomes. From the endosomes, LPL was further routed to the lysosomes, which resulted in a degradation of newly synthesized LPL. Consequently, an 80% reduction of LPL activity was observed in cells that expressed SorLA. By analogy, SorLA regulated the vesicle-like localization of LPL in primary neuronal cells. Thus, LPL binds to SorLA in the biosynthetic pathway and is subsequently transported to endosomes. As a result of this SorLA mediated-transport, newly synthesized LPL can be routed into specialized vesicles and eventually sent to degradation, and its activity thereby regulated.
许多不同的组织和细胞类型表现出脂蛋白脂肪酶（LPL）的调节分泌。然而，迄今为止，LPL 在反式高尔基体网络中的分拣尚未被详细了解。在这里，我们描述了 SorLA（正式称为 SorLA-1 或 SorLA 相关受体）在 LPL 细胞内运输中的作用。我们发现 LPL 在中性和酸性条件下与 SorLA 结合，在细胞中这种结合主要发生在囊泡结构中。SorLA 的表达改变了 LPL 的亚细胞分布，使其在内涵体中更加集中。从内涵体中，LPL 进一步被运送到溶酶体，导致新合成的 LPL 降解。因此，表达 SorLA 的细胞中观察到 LPL 活性降低了 80%。类似地，SorLA 调节原代神经元细胞中 LPL 的囊泡样定位。因此，LPL 在生物合成途径中与 SorLA 结合，随后被运送到内涵体。由于这种 SorLA 介导的运输，新合成的 LPL 可以被定向到专门的囊泡中，并最终被送往降解，从而调节其活性。
