Featured
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Article
| Open Access
Structural mechanism of protein recognition by the FW domain of autophagy receptor Nbr1
Nbr1 recognizes cargos in selective autophagy. Here, authors show filamentous yeast Nbr1 binds Ams1 via an FW domain, and the cryo-EM structure reveals that Nbr1 recognizes the N-terminal di-glycine and tetrameric assembly of Ams1.
- Jianxiu Zhang
- , Ying-Ying Wang
- & Keqiong Ye
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Article
| Open Access
OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection
During herpesvirus infection, most individuals intrinsically suppress a primary infection and therewith preclude potential damage or neurodegeneration of the CNS. Here, Ames et al. show that Optineurin (OPTN), a conserved autophagy receptor, restricts HSV-1 spread, degrades viral VP16 through autophagy and is neuroprotective against HSV infection in vivo.
- Joshua Ames
- , Tejabhiram Yadavalli
- & Deepak Shukla
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Article
| Open Access
Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy
Beneficial and detrimental effects have been ascribed to the different Thrombospondin (Thbs) proteins in the adult mammalian heart. Here, the authors show that Thbs1-mediated activation of PERK-eIF2α-ATF4-induced autophagy regulates adult cardiomyocyte size in the stressed heart.
- Davy Vanhoutte
- , Tobias G. Schips
- & Jeffery D. Molkentin
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Article
| Open Access
Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice
The tau protein has been implicated in neurodegenerative disorders and can propagate from cell to cell. Here, the authors show that tau acetylation reduces its degradation by chaperone-mediated autophagy, causing re-routing to other autophagic pathways and increasing extracellular tau release.
- Benjamin Caballero
- , Mathieu Bourdenx
- & Ana Maria Cuervo
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Article
| Open Access
Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo
Chaperone mediated autophagy (CMA) is selective but its activity in different tissue types has been unclear due to a lack of tools. Here, the authors generate transgenic mice expressing a CMA reporter that provides spatial and temporal in vivo data, uncovering differences in CMA in distinct tissues.
- S. Dong
- , C. Aguirre-Hernandez
- & A. M. Cuervo
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Article
| Open Access
Phosphorylation of ULK1 affects autophagosome fusion and links chaperone-mediated autophagy to macroautophagy
The ULK complex plays a well-known role in initiating autophagy, to recycle cellular components in response to nutritional stress. Here, the authors demonstrate a late role for ULK in auotophagosome–lysosome fusion and provide a direct link between macroautophagy and chaperone mediated autophagy.
- Chenyao Wang
- , Huafei Wang
- & Zhixue Liu
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Article
| Open Access
Phosphorylation of LAMP2A by p38 MAPK couples ER stress to chaperone-mediated autophagy
The endoplasmic reticulum (ER) and lysosome are central to cellular stress responses, but it is unclear how ER stress is signaled to lysosomes. Here the authors show that ER stress activates chaperone-mediated autophagy (CMA) via direct phosphorylation of the CMA receptor LAMP2A by the lysosomal p38 MAPK.
- Wenming Li
- , Jinqiu Zhu
- & Zixu Mao
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Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage
Chaperone-mediated autophagy (CMA) helps maintain protein quality during cellular stress. Here the authors show that CMA is also activated in response to DNA damage and regulates degradation of the cell cycle regulator Chk1—the first nuclear protein shown to be a substrate of CMA.
- Caroline Park
- , Yousin Suh
- & Ana Maria Cuervo
Targeting retinoic acid receptor alpha-corepressor interaction activates chaperone-mediated autophagy and protects against retinal degeneration