Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex

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Beclin 1 was not only the first-described mammalian autophagy protein, but is one of the most widely-characterized players in autophagy regulation. It is implicated in multiple human disease conditions. As a core component of the essential lipid kinase complex (PI3K-III), beclin 1 has largely been characterized to date in the context of autophagy through its recruitment of additional autophagy proteins for the assembly of the PI3K-III complexes involved in the nucleation of the autophagosome. Little is known, however, about how beclin 1 regulates specific functions of PI3K-III in other membrane trafficking pathways. Furthermore, although beclin 1 has been linked to multiple neurodegenerative diseases, the function of beclin 1 in the brain remains uncharacterized. Herein, we used genetic animal models and mutant cell lines to demonstrate that beclin 1 participates in multiple organelle trafficking pathways. Beclin 1 deficiency in neurons causes severe neurodegeneration, concomitant with aberrant late endosome formation and impaired phospholipid localization. Our mechanistic study reveals the essential role for beclin 1 in neuron survival involving multiple membrane trafficking pathways including endocytosis and autophagy. Our study clarifies the physiological function of beclin 1, which leads for further understanding of its role in tumorigenesis, infectious disease and neurodegenerative disease.

Vyšlo v časopise: Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004626
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004626

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