Divergent roles of BECN1 in LC3 lipidation and autophagosomal function
| Autor: | Fang Xu, Wensheng Wei, Pengfei Yuan, J. J. Peng, Ruina He |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Autophagosome
PIK3R4/VPS15 phosphoinositide-3-kinase regulatory subunit 4 autophagy PIK3C3/VPS34 phosphatidylinositol 3-kinase catalytic subunit type 3 UVRAG UV radiation resistance associated BECN1 Beclin 1 autophagy related autophagosome ATG autophagy related Lipid-anchored protein TUBB tubulin β class I Biology BCL2-like 1 BECN1P1/BECN2 Beclin 1 autophagy related pseudogene 1 chemistry.chemical_compound MAP1LC3/LC3 microtubule-associated protein 1 light chain 3 TALEN transcription activator-like effector nuclease LC3 Phosphatidylinositol Molecular Biology MAP1LC3-I/LC3-I soluble proteolytically processed microtubule-associated protein 1 light chain 3 MAP1LC3B/LC3B microtubule-associated protein 1 light chain 3 β SQSTM1/p62 sequestosome 1 Phagosome GFP green fluorescent protein EM electron microscopy KO knockout BCL2L1/Bcl-xL BCL2-like 1 Autophagy Basic Brief Report BafA1 bafilomycin A1 Cell Biology BECN1 Cell biology PtdIns3K ZFYVE1/DFCP1 zinc finger FYVE domain containing 1 chemistry GAPDH glyceraldehyde-3-phosphate dehydrogenase MAP1LC3B MAP1LC3-II/LC3-II proteolytically processed and lipid-modified microtubule-associated protein 1 light chain 3 PtdIns3K phosphatidylinositol 3-kinase |
| Zdroj: | Autophagy |
| DOI: | 10.6084/m9.figshare.1408685.v3 |
| Popis: | BECN1/Beclin 1 is regarded as a critical component in the class III phosphatidylinositol 3-kinase (PtdIns3K) complex to trigger autophagy in mammalian cells. Despite its significant role in a number of cellular and physiological processes, the exact function of BECN1 in autophagy remains controversial. Here we created a BECN1 knockout human cell line using the TALEN technique. Surprisingly, the complete loss of BECN1 had little effect on LC3 (MAP1LC3B/LC3B) lipidation, and LC3B puncta resembling autophagosomes by fluorescence microscopy were still evident albeit significantly smaller than those in the wild-type cells. Electron microscopy (EM) analysis revealed that BECN1 deficiency led to malformed autophagosome-like structures containing multiple layers of membranes under amino acid starvation. We further confirmed that the PtdIns3K complex activity and autophagy flux were disrupted in BECN1−/− cells. Our results demonstrate the essential role of BECN1 in the functional formation of autophagosomes, but not in LC3B lipidation. |
| Databáze: | OpenAIRE |
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