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Publication : Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors.

First Author  Zhou P Year  2007
Journal  Neuron Volume  55
Issue  1 Pages  53-68
PubMed ID  17610817 Mgi Jnum  J:128625
Mgi Id  MGI:3767721 Doi  10.1016/j.neuron.2007.05.030
Citation  Zhou P, et al. (2007) Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron 55(1):53-68
abstractText  During development, neural precursors migrate in response to positional cues such as growth factor gradients. However, the mechanisms that enable precursors to sense and respond to such gradients are poorly understood. Here we show that cerebellar granule cell precursors (GCPs) migrate along a gradient of brain-derived neurotrophic factor (BDNF), and we demonstrate that vesicle trafficking is critical for this chemotactic process. Activation of TrkB, the BDNF receptor, stimulates GCPs to secrete BDNF, thereby amplifying the ambient gradient. The BDNF gradient stimulates endocytosis of TrkB and associated signaling molecules, causing asymmetric accumulation of signaling endosomes at the subcellular location where BDNF concentration is maximal. Thus, regulated BDNF exocytosis and TrkB endocytosis enable precursors to polarize and migrate in a directed fashion along a shallow BDNF gradient.
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