Department of Neuroscience, Jefferson Center for Synaptic Biology, Vickie and Jack Farber Institute for Neuroscience, Sydney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Neuroscience, Jefferson Center for Synaptic Biology, Vickie and Jack Farber Institute for Neuroscience, Sydney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cell Rep. 2022 Apr 26;39(4):110748. doi: 10.1016/j.celrep.2022.110748.
Development and function of nerve cells rely on the orchestration of microtubule-based transport from the cell body into distal axonal terminals. Neurons often have highly elaborate branches innervating multiple targets, but how protein or membrane cargos navigate through branch junctions to specific branch targets is unknown. Here, we demonstrate that anterograde transport of membrane vesicles through axonal branch junctions is highly selective, which is influenced by branch length and more strongly by growth cone motility. Using an optogenetic tool, we demonstrate that signaling from the growth cone can rapidly direct transport through branch junctions. We further demonstrate that such transport selectivity is differentially regulated for different vesicles and mediated by the KIF1/kinesin-3 family motors. We propose that this transport regulation through branch junctions could broadly impact neuronal development, function, and regeneration.
神经细胞的发育和功能依赖于细胞体到远端轴突末端的基于微管的运输的协调。神经元通常具有高度精细的分支，支配多个靶标，但蛋白质或膜货物如何通过分支连接点导航到特定的分支靶标尚不清楚。在这里，我们证明了膜囊泡通过轴突分支连接点的正向运输具有高度选择性，这受分支长度的影响，受生长锥运动的影响更大。使用光遗传学工具，我们证明来自生长锥的信号可以快速指导通过分支连接点的运输。我们进一步证明，这种运输选择性对于不同的囊泡是不同的，并由 KIF1/驱动蛋白-3 家族的马达介导。我们提出，这种通过分支连接点的运输调节可能会广泛影响神经元的发育、功能和再生。
