Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/36226
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | - |
dc.creator | McKnight, NC | - |
dc.creator | Zhong, Y | - |
dc.creator | Wold, MS | - |
dc.creator | Gong, SC | - |
dc.creator | Phillips, GR | - |
dc.creator | Dou, ZX | - |
dc.creator | Zhao, YX | - |
dc.creator | Heintz, N | - |
dc.creator | Zong, WX | - |
dc.creator | Yue, ZY | - |
dc.date.accessioned | 2016-04-15T08:36:50Z | - |
dc.date.available | 2016-04-15T08:36:50Z | - |
dc.identifier.issn | 1553-7390 (print) | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/36226 | - |
dc.language.iso | en | en_US |
dc.publisher | Public Library of Science | en_US |
dc.rights | © 2014 McKnight et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_US |
dc.rights | The following publication: McKnight NC, Zhong Y, Wold MS, Gong S, Phillips GR, Dou Z, et al. (2014) Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex. PLoS Genet 10(10): e1004626 is available at https://doi.org/10.1371/journal.pgen.1004626 | en_US |
dc.title | Beclin 1 is required for neuron viability and regulates endosome pathways via the UVRAG-VPS34 complex | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.volume | 10 | en_US |
dc.identifier.issue | 10 | en_US |
dc.identifier.doi | 10.1371/journal.pgen.1004626 | en_US |
dcterms.abstract | Deficiency of autophagy protein beclin 1 is implicated in tumorigenesis and neurodegenerative diseases, but the molecular mechanism remains elusive. Previous studies showed that Beclin 1 coordinates the assembly of multiple VPS34 complexes whose distinct phosphatidylinositol 3-kinase III (PI3K-III) lipid kinase activities regulate autophagy at different steps. Recent evidence suggests a function of beclin 1 in regulating multiple VPS34-mediated trafficking pathways beyond autophagy; however, the precise role of beclin 1 in autophagy-independent cellular functions remains poorly understood. Herein we report that beclin 1 regulates endocytosis, in addition to autophagy, and is required for neuron viability in vivo. We find that neuronal beclin 1 associates with endosomes and regulates EEA1/early endosome localization and late endosome formation. Beclin 1 maintains proper cellular phosphatidylinositol 3-phosphate (PI(3) P) distribution and total levels, and loss of beclin 1 causes a disruption of active Rab5 GTPase-associated endosome formation and impairment of endosome maturation, likely due to a failure of Rab5 to recruit VPS34. Furthermore, we find that Beclin 1 deficiency causes complete loss of the UVRAG-VPS34 complex and associated lipid kinase activity. Interestingly, beclin 1 deficiency impairs p40 phox linked endosome formation, which is rescued by overexpressed UVRAG or beclin 1, but not by a coiled-coil domain-truncated beclin 1 (a UVRAG-binding mutant), Atg14L or RUBICON. Thus, our study reveals the essential role for beclin 1 in neuron survival involving multiple membrane trafficking pathways including endocytosis and autophagy, and suggests that the UVRAG-beclin 1 interaction underlies beclin 1's function in endocytosis. | - |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Plos genetics, 2014, v. 10, no. 10, e1004626 | - |
dcterms.isPartOf | Plos genetics | - |
dcterms.issued | 2014 | - |
dc.identifier.isi | WOS:000344650700015 | - |
dc.identifier.scopus | 2-s2.0-84908321680 | - |
dc.identifier.pmid | 25275521 | - |
dc.identifier.rosgroupid | 2014004781 | - |
dc.description.ros | 2014-2015 > Academic research: refereed > Publication in refereed journal | en_US |
dc.description.validate | 201810_a bcma | en_US |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | OA_IR/PIRA | en_US |
dc.description.pubStatus | Published | en_US |
dc.description.oaCategory | CC | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
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McKnight_Beclin 1_neuron_viability.PDF | 2.76 MB | Adobe PDF | View/Open |
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