Farías Ginny G, Guardia Carlos M, Britt Dylan J, Guo Xiaoli, Bonifacino Juan S
Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA.
Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA.
Cell Rep. 2015 Nov 10;13(6):1221-1232. doi: 10.1016/j.celrep.2015.09.074. Epub 2015 Oct 29.
Polarized sorting of newly synthesized proteins to the somatodendritic and axonal domains of neurons occurs by selective incorporation into distinct populations of vesicular transport carriers. An unresolved issue is how the vesicles themselves are sorted to their corresponding neuronal domains. Previous studies concluded that the axon initial segment (AIS) is an actin-based filter that selectively prevents passage of somatodendritic vesicles into the axon. We find, however, that most somatodendritic vesicles fail to enter the axon at a more proximal region in the axon hillock, herein referred to as the pre-axonal exclusion zone (PAEZ). Forced coupling of a somatodendritic cargo protein to an axonally directed kinesin is sufficient to drive transport of whole somatodendritic vesicles through the PAEZ toward the distal axon. Based on these findings, we propose that polarized sorting of transport vesicles occurs at the PAEZ and depends on the ability of the vesicles to acquire an appropriately directed microtubule motor.
新合成的蛋白质向神经元的树突体和轴突区域进行极化分选，是通过选择性地整合到不同的囊泡运输载体群体中实现的。一个尚未解决的问题是囊泡本身如何被分选到其相应的神经元区域。先前的研究得出结论，轴突起始段（AIS）是一个基于肌动蛋白的过滤器，可选择性地阻止树突体囊泡进入轴突。然而，我们发现，大多数树突体囊泡在轴丘中更靠近近端的区域无法进入轴突，在此称为轴突前排除区（PAEZ）。将树突体货物蛋白与轴突定向驱动蛋白强制偶联足以驱动整个树突体囊泡通过PAEZ向轴突远端运输。基于这些发现，我们提出运输囊泡的极化分选发生在PAEZ，并且取决于囊泡获得适当定向的微管马达的能力。
