Different ER-plasma membrane tethers play opposing roles in autophagy of the cortical ER

• 成果类型: Article
• 署名作者: Liu, Dongmei; Yuan, Hua; Chen, Shuliang; Ferro-Novick, Susan; Novick, Peter
• 署名单位: University of California System; University of California San Diego
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11366
• DOI: 10.1073/pnas.2321991121
• 发表日期: 2024-06-11
• 关键词: reticulum-associated degradation; endoplasmic-reticulum; contact; protein; ORGANIZATION; endocytosis; receptor; sites; yeast

摘要

The endoplasmic reticulum (ER) undergoes degradation by selective macroautophagy (ER - phagy) in response to starvation or the accumulation of misfolded proteins within its lumen. In yeast, actin assembly at sites of contact between the cortical ER (cER) and endocytic pits acts to displace elements of the ER from their association with the plasma membrane (PM) so they can interact with the autophagosome assembly machinery near the vacuole. A collection of proteins tether the cER to the PM. Of these, Scs2/22 and Ist2 are required for cER - phagy, most likely through their roles in lipid transport, while deletion of the tricalbins, TCB1 / 2 /3, bypasses those requirements. An artificial ER-PM tether blocks cER - phagy in both the wild type (WT) and a strain lacking endogenous tethers, supporting the importance of cER displacement from the PM. Scs2 and Ist2 can be cross - linked to the selective cER - phagy receptor, Atg40. The COPII cargo adaptor subunit, Lst1, associates with Atg40 and is required for cER - phagy. This requirement is also bypassed by deletion of the ER-PM tethers, suggesting a role for Lst1 prior to the displacement of the cER from the PM during cER - phagy. Although pexophagy and mitophagy also require actin assembly, deletion of ER-PM tethers does not bypass those requirements. We propose that within the context of rapamycin - induced cER - phagy, Scs2/22, Ist2, and Lst1 promote the local displacement of an element of the cER from the cortex, while Tcb1/2/3 act in opposition, anchoring the cER to the plasma membrane.