title: Beclin 1 regulates neuronal transforming growth factor-β signaling by mediating recycling of the type I receptor ALK5.
abstract: BACKGROUND
  Beclin 1 is a key regulator of multiple trafficking pathways, including autophagy and receptor recycling in yeast and microglia. Decreased beclin 1 levels in the CNS result in neurodegeneration, an effect attributed to impaired autophagy. However, neurons also rely heavily on trophic factors, and signaling through these pathways requires the proper trafficking of trophic factor receptors.
  
  
  RESULTS
  We discovered that beclin 1 regulates signaling through the neuroprotective TGF-β pathway. Beclin 1 is required for recycling of the type I TGF-β receptor ALK5. We show that beclin 1 recruits the retromer to ALK5 and facilitates its localization to Rab11(+) endosomes. Decreased levels of beclin 1, or its binding partners VPS34 and UVRAG, impair TGF-β signaling.
  
  
  CONCLUSIONS
  These findings identify beclin 1 as a positive regulator of a trophic signaling pathway via receptor recycling, and suggest that neuronal death induced by decreased beclin 1 levels may also be due to impaired trophic factor signaling.
authors.affiliation: Cell and Molecular Biology Program, Department of Biology, Stanford University, Stanford, CA, 94305, USA. ceobrien@stanford.edu.|Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA. ceobrien@stanford.edu.|Center for Tissue Regeneration, Repair, and Restoration, Veteran Administration Palo Alto Health Care System, Palo Alto, CA, 94304, USA. ceobrien@stanford.edu.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: O'Brien
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA. lianab@stanford.edu.|Center for Tissue Regeneration, Repair, and Restoration, Veteran Administration Palo Alto Health Care System, Palo Alto, CA, 94304, USA. lianab@stanford.edu.|Graduate Program in Neuroscience, Stanford University School of Medicine, Stanford, CA, 94305, USA. lianab@stanford.edu.
authors.forename: Liana
authors.initials: L
authors.lastname: Bonanno
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA. huizhang@stanford.edu.|Center for Tissue Regeneration, Repair, and Restoration, Veteran Administration Palo Alto Health Care System, Palo Alto, CA, 94304, USA. huizhang@stanford.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA. twc@stanford.edu.|Center for Tissue Regeneration, Repair, and Restoration, Veteran Administration Palo Alto Health Care System, Palo Alto, CA, 94304, USA. twc@stanford.edu.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology; D000071186:Beclin-1; D011992:Endosomes / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse