Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5862-7. doi: 10.1073/pnas.1113819109. Epub 2012 Mar 26.
Presynaptic nerve terminals are formed from preassembled vesicles that are delivered to the prospective synapse by kinesin-mediated axonal transport. However, precisely how the various cargoes are linked to the motor proteins remains unclear. Here, we report a transport complex linking syntaxin 1a (Stx) and Munc18, two proteins functioning in synaptic vesicle exocytosis at the presynaptic plasma membrane, to the motor protein Kinesin-1 via the kinesin adaptor FEZ1. Mutation of the FEZ1 ortholog UNC-76 in Caenorhabditis elegans causes defects in the axonal transport of Stx. We also show that binding of FEZ1 to Kinesin-1 and Munc18 is regulated by phosphorylation, with a conserved site (serine 58) being essential for binding. When expressed in C. elegans, wild-type but not phosphorylation-deficient FEZ1 (S58A) restored axonal transport of Stx. We conclude that FEZ1 operates as a kinesin adaptor for the transport of Stx, with cargo loading and unloading being regulated by protein kinases.
突触前神经末梢是由预先组装的囊泡形成的，这些囊泡通过驱动蛋白介导的轴突运输被运送到潜在的突触。然而，各种货物与运动蛋白是如何连接的仍然不清楚。在这里，我们报告了一个运输复合物，它将突触小泡胞吐作用中在突触前质膜上起作用的两种蛋白 syntaxin 1a（Stx）和 Munc18 与运动蛋白 Kinesin-1 通过 kinesin 接头 FEZ1 连接起来。秀丽隐杆线虫中 FEZ1 同源物 UNC-76 的突变导致 Stx 的轴突运输缺陷。我们还表明，FEZ1 与 Kinesin-1 和 Munc18 的结合受磷酸化调节，保守位点（丝氨酸 58）对于结合是必不可少的。当在秀丽隐杆线虫中表达时，野生型但不是磷酸化缺陷型 FEZ1（S58A）恢复了 Stx 的轴突运输。我们的结论是，FEZ1 作为 Stx 运输的驱动蛋白接头发挥作用，货物的装载和卸载受蛋白激酶调节。
