Wisco Dolora, Anderson Eric D, Chang Michael C, Norden Caren, Boiko Tatiana, Fölsch Heike, Winckler Bettina
Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Cell Biol. 2003 Sep 29;162(7):1317-28. doi: 10.1083/jcb.200307069.
Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of NgCAM kinetically, surprisingly we observed a transient appearance of NgCAM on the somatodendritic plasma membrane. Down-regulation of endocytosis resulted in loss of axonal accumulation of NgCAM, indicating that the axonal localization of NgCAM was dependent on endocytosis. Our data suggest the existence of a dendrite-to-axon transcytotic pathway to achieve axonal accumulation. NgCAM mutants with a point mutation in a crucial cytoplasmic tail motif (YRSL) are unable to access the transcytotic route. Instead, they were found to travel to the axon on a direct route. Therefore, our results suggest that multiple distinct pathways operate in hippocampal neurons to achieve axonal accumulation of membrane proteins.
神经元极性至少部分是由膜蛋白向不同区域（如轴突和胞体/树突）的差异分选介导的。我们研究了NgCAM（一种存在于轴突质膜上的细胞粘附分子）亚细胞靶向的潜在途径。在动力学上追踪NgCAM的运输过程时，令人惊讶的是，我们观察到NgCAM在树突状质膜上短暂出现。内吞作用的下调导致NgCAM在轴突中的积累丧失，这表明NgCAM的轴突定位依赖于内吞作用。我们的数据表明存在一条从树突到轴突的转胞吞途径以实现轴突积累。在关键的细胞质尾部基序（YRSL）中存在点突变的NgCAM突变体无法进入转胞吞途径。相反，它们被发现是通过直接途径运输到轴突的。因此，我们的结果表明，在海马神经元中存在多种不同的途径来实现膜蛋白的轴突积累。
