Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 6, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2117554119
Keywords
autophagy; endoplasmic reticulum; actin
Categories
Funding
- NIH [GM35370, 5R35GM131681]
- ZonMW TOP [91217002]
- Open Competition ENW-KLEIN [OCENW.KLEIN.118]
- Marie Sklodowska Curie ETN [765912]
- Marie Sklodowska-Curie Cofund [713660]
- Aard-en Levenswetenschappen open program [ALWOP.355]
- Marie Curie Actions (MSCA) [713660] Funding Source: Marie Curie Actions (MSCA)
Ask authors/readers for more resources
This study discovered a process called ER-phagy, which selectively delivers fragments of the endoplasmic reticulum to the lysosome or vacuole in response to starvation or the accumulation of misfolded proteins. The loss of specific genes and proteins blocks the association between the autophagy receptor and the assembly scaffold protein, and a membrane contact site module is also found to be involved in ER-phagy.
Fragments of the endoplasmic reticulum (ER) are selectively delivered to the lysosome (mammals) or vacuole (yeast) in response to starvation or the accumulation of misfolded proteins through an autophagic process known as ER-phagy. A screen of the Saccharomyces cerevisiae deletion library identified end3 Delta as a candidate knockout strain that is defective in ER-phagy during starvation conditions, but not bulk autophagy. We find that loss of End3 and its stable binding partner Pan1, or inhibition of the Arp2/3 complex that is coupled by the End3-Pan1 complex to endocytic pits, blocks the association of the cortical ER autophagy receptor, Atg40, with the autophagosomal assembly scaffold protein Atg11. The membrane contact site module linking the rim of cortical ER sheets and endocytic pits, consisting of Scs2 or Scs22, Osh2 or Osh3, and Myo3 or Myo5, is also needed for ER-phagy. Both Atg40 and Scs2 are concentrated at the edges of ER sheets and can be cross-linked to each other. Our results are consistent with a model in which actin assembly at sites of contact between the cortical ER and endocytic pits contributes to ER sequestration into autophagosomes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available