Hazuka C D, Foletti D L, Hsu S C, Kee Y, Hopf F W, Scheller R H
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5428, USA.
J Neurosci. 1999 Feb 15;19(4):1324-34. doi: 10.1523/JNEUROSCI.19-04-01324.1999.
The molecules that specify domains on the neuronal plasma membrane for the delivery and accumulation of vesicles during neurite outgrowth and synapse formation are unknown. We investigated the role of the sec6/8 complex, a set of proteins that specifies vesicle targeting sites in yeast and epithelial cells, in neuronal membrane trafficking. This complex was found in layers of developing rat brain undergoing synaptogenesis. In cultured hippocampal neurons, the sec6/8 complex was present in regions of ongoing membrane addition: the tips of growing neurites, filopodia, and growth cones. In young axons, the sec6/8 complex was also confined to periodic domains of the plasma membrane. The distribution of synaptotagmin, synapsin1, sec6, and FM1-43 labeling in cultured neurons suggested that the plasma membrane localization of the sec6/8 complex preceded the arrival of synaptic markers and was downregulated in mature synapses. We propose that the sec6/8 complex specifies sites for targeting vesicles at domains of neurite outgrowth and potential active zones during synaptogenesis.
在神经突生长和突触形成过程中,用于囊泡运输和积累的、在神经元质膜上指定区域的分子尚不清楚。我们研究了sec6/8复合体(一组在酵母和上皮细胞中指定囊泡靶向位点的蛋白质)在神经元膜运输中的作用。在正在进行突触形成的发育中大鼠脑层中发现了这种复合体。在培养的海马神经元中,sec6/8复合体存在于正在进行膜添加的区域:生长神经突的尖端、丝状伪足和生长锥。在幼嫩轴突中,sec6/8复合体也局限于质膜的周期性区域。培养神经元中突触结合蛋白、突触素1、sec6和FM1-43标记的分布表明,sec6/8复合体在质膜上的定位先于突触标记物的到达,并且在成熟突触中下调。我们提出,sec6/8复合体在突触形成过程中,在神经突生长区域和潜在的活性区指定囊泡靶向位点。