Klinger Stine C, Højland Anne, Jain Shweta, Kjolby Mads, Madsen Peder, Svendsen Anna Dorst, Olivecrona Gunilla, Bonifacino Juan S, Nielsen Morten S
Department of Biomedicine, The Lundbeck Foundation Initiative on Brain Barriers and Drug Delivery, Aarhus University, Denmark.
Department of Biomedicine, The MIND Centre, Aarhus University, Denmark.
FEBS J. 2016 Jul;283(13):2476-93. doi: 10.1111/febs.13758. Epub 2016 Jun 6.
The sorting receptor SorLA is highly expressed in neurons and is also found in other polarized cells. The receptor has been reported to participate in the trafficking of several ligands, some of which are linked to human diseases, including the amyloid precursor protein, TrkB, and Lipoprotein Lipase (LpL). Despite this, only the trafficking in nonpolarized cells has been described so far. Due to the many differences between polarized and nonpolarized cells, we examined the localization and trafficking of SorLA in epithelial Madin-Darby canine kidney (MDCK) cells and rat hippocampal neurons. We show that SorLA is mainly found in sorting endosomes and on the basolateral surface of MDCK cells and in the somatodendritic domain of neurons. This polarized distribution of SorLA respectively depends on an acidic cluster and an extended version of this cluster and involves the cellular adaptor complex AP-1. Furthermore, we show that SorLA can mediate transcytosis across a tight cell layer.
分选受体SorLA在神经元中高度表达，在其他极化细胞中也有发现。据报道，该受体参与多种配体的运输，其中一些配体与人类疾病有关，包括淀粉样前体蛋白、酪氨酸激酶受体B（TrkB）和脂蛋白脂肪酶（LpL）。尽管如此，迄今为止仅描述了其在非极化细胞中的运输情况。由于极化细胞和非极化细胞之间存在许多差异，我们研究了SorLA在上皮性犬肾（MDCK）细胞和大鼠海马神经元中的定位和运输。我们发现，SorLA主要存在于MDCK细胞的分选内体和基底外侧表面以及神经元的树突状区域。SorLA的这种极化分布分别依赖于一个酸性簇及其扩展形式，并且涉及细胞衔接蛋白复合物AP-1。此外，我们还表明SorLA可以介导跨紧密细胞层的转胞吞作用。
