title: Snapin recruits dynein to BDNF-TrkB signaling endosomes for retrograde axonal transport and is essential for dendrite growth of cortical neurons.
abstract: Neurotrophin signaling is crucial for neuron growth. While the "signaling endosomes" hypothesis is one of the accepted models, the molecular machinery that drives retrograde axonal transport of TrkB signaling endosomes is largely unknown. In particular, mechanisms recruiting dynein to TrkB signaling endosomes have not been elucidated. Here, using snapin deficient mice and gene rescue experiments combined with compartmentalized cultures of live cortical neurons, we reveal that Snapin, as a dynein adaptor, mediates retrograde axonal transport of TrkB signaling endosomes. Such a role is essential for dendritic growth of cortical neurons. Deleting snapin or disrupting Snapin-dynein interaction abolishes TrkB retrograde transport, impairs BDNF-induced retrograde signaling from axonal terminals to the nucleus, and decreases dendritic growth. Such defects were rescued by reintroducing the snapin gene. Our study indicates that Snapin-dynein coupling is one of the primary mechanisms driving BDNF-TrkB retrograde transport, thus providing mechanistic insights into the regulation of neuronal growth and survival.
authors: Synaptic Functions Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2B-215, 35 Convent Drive, Bethesda, MD 20892-3706, USA.
authors: Bing
authors: B
authors: Zhou
authors: Qian
authors: Q
authors: Cai
authors: Yuxiang
authors: Y
authors: Xie
authors: Zu-Hang
authors: ZH
authors: Sheng
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D004398:Dyneins / Q000378:metabolism*; D004622:Embryo, Mammalian; D011992:Endosomes / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C498451:Snapin protein, mouse; D033921:Vesicular Transport Proteins; D020813:Receptor, trkB; D004398:Dyneins