Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Mechanisms that turn over components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope-localized cargo adaptor, Atg39. A split-GFP reporter showed t...
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| Veröffentlicht in: | The Journal of cell biology 2021-12, Vol.220 (12), p.1 |
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| creator | Chandra, Sunandini Mannino, Philip J Thaller, David J Ader, Nicholas R King, Megan C Melia, Thomas J Lusk, C Patrick |
| description | Mechanisms that turn over components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope-localized cargo adaptor, Atg39. A split-GFP reporter showed that Atg39 localizes to the outer nuclear membrane (ONM) and thus targets the INM across the nuclear envelope lumen. Consistent with this, sequence elements that confer both nuclear envelope localization and a membrane remodeling activity are mapped to the Atg39 lumenal domain; these lumenal motifs are required for the autophagy-mediated degradation of integral INM proteins. Interestingly, correlative light and electron microscopy shows that the overexpression of Atg39 leads to the expansion of the ONM and the enclosure of a network of INM-derived vesicles in the nuclear envelope lumen. Thus, we propose an outside-in model of nucleophagy where INM is delivered into vesicles in the nuclear envelope lumen, which can be targeted by the autophagosome. |
| doi_str_mv | 10.1083/jcb.202103030 |
| format | Article |
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We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope-localized cargo adaptor, Atg39. A split-GFP reporter showed that Atg39 localizes to the outer nuclear membrane (ONM) and thus targets the INM across the nuclear envelope lumen. Consistent with this, sequence elements that confer both nuclear envelope localization and a membrane remodeling activity are mapped to the Atg39 lumenal domain; these lumenal motifs are required for the autophagy-mediated degradation of integral INM proteins. Interestingly, correlative light and electron microscopy shows that the overexpression of Atg39 leads to the expansion of the ONM and the enclosure of a network of INM-derived vesicles in the nuclear envelope lumen. Thus, we propose an outside-in model of nucleophagy where INM is delivered into vesicles in the nuclear envelope lumen, which can be targeted by the autophagosome.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.202103030</identifier><identifier>PMID: 34714326</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Autophagosomes - metabolism ; Autophagosomes - ultrastructure ; Autophagy ; Autophagy-Related Proteins - chemistry ; Autophagy-Related Proteins - metabolism ; Cell Death and Autophagy ; Cytoplasmic Vesicles - metabolism ; Cytoplasmic Vesicles - ultrastructure ; Electron microscopy ; Green Fluorescent Proteins - metabolism ; Localization ; Membrane and Lipid Biology ; Membrane vesicles ; Membranes ; Nuclear Envelope - metabolism ; Nuclear Envelope - ultrastructure ; Phagocytosis ; Protein Domains ; Receptors, Cytoplasmic and Nuclear - chemistry ; Receptors, Cytoplasmic and Nuclear - metabolism ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae - ultrastructure ; Saccharomyces cerevisiae Proteins - chemistry ; Saccharomyces cerevisiae Proteins - metabolism ; Structure-Activity Relationship ; Time Factors ; Vacuoles - metabolism ; Vacuoles - ultrastructure ; Vesicles ; Vesicular Transport Proteins - metabolism</subject><ispartof>The Journal of cell biology, 2021-12, Vol.220 (12), p.1</ispartof><rights>2021 Chandra et al.</rights><rights>Copyright Rockefeller University Press Dec 2021</rights><rights>2021 Chandra et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-c3e335abd30967c6dfc4f41d930fc0b1f6300a5c037f99fe1a0ce2ca862bcf7d3</citedby><cites>FETCH-LOGICAL-c415t-c3e335abd30967c6dfc4f41d930fc0b1f6300a5c037f99fe1a0ce2ca862bcf7d3</cites><orcidid>0000-0003-4703-0533 ; 0000-0001-6950-2314 ; 0000-0002-1688-2226 ; 0000-0001-7744-4484 ; 0000-0002-5798-4624 ; 0000-0001-5386-0934 ; 0000-0003-3577-5562</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34714326$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chandra, Sunandini</creatorcontrib><creatorcontrib>Mannino, Philip J</creatorcontrib><creatorcontrib>Thaller, David J</creatorcontrib><creatorcontrib>Ader, Nicholas R</creatorcontrib><creatorcontrib>King, Megan C</creatorcontrib><creatorcontrib>Melia, Thomas J</creatorcontrib><creatorcontrib>Lusk, C Patrick</creatorcontrib><title>Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Mechanisms that turn over components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope-localized cargo adaptor, Atg39. A split-GFP reporter showed that Atg39 localizes to the outer nuclear membrane (ONM) and thus targets the INM across the nuclear envelope lumen. Consistent with this, sequence elements that confer both nuclear envelope localization and a membrane remodeling activity are mapped to the Atg39 lumenal domain; these lumenal motifs are required for the autophagy-mediated degradation of integral INM proteins. Interestingly, correlative light and electron microscopy shows that the overexpression of Atg39 leads to the expansion of the ONM and the enclosure of a network of INM-derived vesicles in the nuclear envelope lumen. Thus, we propose an outside-in model of nucleophagy where INM is delivered into vesicles in the nuclear envelope lumen, which can be targeted by the autophagosome.</description><subject>Autophagosomes - metabolism</subject><subject>Autophagosomes - ultrastructure</subject><subject>Autophagy</subject><subject>Autophagy-Related Proteins - chemistry</subject><subject>Autophagy-Related Proteins - metabolism</subject><subject>Cell Death and Autophagy</subject><subject>Cytoplasmic Vesicles - metabolism</subject><subject>Cytoplasmic Vesicles - ultrastructure</subject><subject>Electron microscopy</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Localization</subject><subject>Membrane and Lipid Biology</subject><subject>Membrane vesicles</subject><subject>Membranes</subject><subject>Nuclear Envelope - metabolism</subject><subject>Nuclear Envelope - ultrastructure</subject><subject>Phagocytosis</subject><subject>Protein Domains</subject><subject>Receptors, Cytoplasmic and Nuclear - chemistry</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae - ultrastructure</subject><subject>Saccharomyces cerevisiae Proteins - chemistry</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>Time Factors</subject><subject>Vacuoles - metabolism</subject><subject>Vacuoles - ultrastructure</subject><subject>Vesicles</subject><subject>Vesicular Transport Proteins - metabolism</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUFr3DAQhUVoSbZpj70WQS-5OBlZkmVfAiE0bSGQS3IWsjza9SJbG0le2H9flaRLUuYwMPPxmDePkK8MLhm0_Gpr-8saaga81AlZMSmgapmAD2QFZV51spZn5FNKWwAQSvBTcsaFYoLXzYqMN3nNO5rQo83jHv2BWrPLS8REx3nGSOfFejSRTjj10cxYxjlQv0w4G0_3mMayT9SFSAf0RSIeaAHyBqlZcthtzDqkMOFn8tEZn_DLaz8nT3c_Hm9_VfcPP3_f3txXVjCZK8uRc2n6gUPXKNsMzgon2NBxcBZ65hoOYKQFrlzXOWQGLNbWtE3dW6cGfk6uX3R3Sz_hYHHO0Xi9i-Nk4kEHM-r3m3nc6HXY61YqCawtAhevAjE8L5iynsZk0ftiPixJ17IDxlTbqoJ-_w_dhiWWvxSqAclB1AoKVb1QNoaUIrrjMQz03xB1CVEfQyz8t7cOjvS_1Pgf_sCahQ</recordid><startdate>20211206</startdate><enddate>20211206</enddate><creator>Chandra, Sunandini</creator><creator>Mannino, Philip J</creator><creator>Thaller, David J</creator><creator>Ader, Nicholas R</creator><creator>King, Megan C</creator><creator>Melia, Thomas J</creator><creator>Lusk, C Patrick</creator><general>Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4703-0533</orcidid><orcidid>https://orcid.org/0000-0001-6950-2314</orcidid><orcidid>https://orcid.org/0000-0002-1688-2226</orcidid><orcidid>https://orcid.org/0000-0001-7744-4484</orcidid><orcidid>https://orcid.org/0000-0002-5798-4624</orcidid><orcidid>https://orcid.org/0000-0001-5386-0934</orcidid><orcidid>https://orcid.org/0000-0003-3577-5562</orcidid></search><sort><creationdate>20211206</creationdate><title>Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome</title><author>Chandra, Sunandini ; 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We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope-localized cargo adaptor, Atg39. A split-GFP reporter showed that Atg39 localizes to the outer nuclear membrane (ONM) and thus targets the INM across the nuclear envelope lumen. Consistent with this, sequence elements that confer both nuclear envelope localization and a membrane remodeling activity are mapped to the Atg39 lumenal domain; these lumenal motifs are required for the autophagy-mediated degradation of integral INM proteins. Interestingly, correlative light and electron microscopy shows that the overexpression of Atg39 leads to the expansion of the ONM and the enclosure of a network of INM-derived vesicles in the nuclear envelope lumen. Thus, we propose an outside-in model of nucleophagy where INM is delivered into vesicles in the nuclear envelope lumen, which can be targeted by the autophagosome.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>34714326</pmid><doi>10.1083/jcb.202103030</doi><orcidid>https://orcid.org/0000-0003-4703-0533</orcidid><orcidid>https://orcid.org/0000-0001-6950-2314</orcidid><orcidid>https://orcid.org/0000-0002-1688-2226</orcidid><orcidid>https://orcid.org/0000-0001-7744-4484</orcidid><orcidid>https://orcid.org/0000-0002-5798-4624</orcidid><orcidid>https://orcid.org/0000-0001-5386-0934</orcidid><orcidid>https://orcid.org/0000-0003-3577-5562</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Autophagosomes - metabolism Autophagosomes - ultrastructure Autophagy Autophagy-Related Proteins - chemistry Autophagy-Related Proteins - metabolism Cell Death and Autophagy Cytoplasmic Vesicles - metabolism Cytoplasmic Vesicles - ultrastructure Electron microscopy Green Fluorescent Proteins - metabolism Localization Membrane and Lipid Biology Membrane vesicles Membranes Nuclear Envelope - metabolism Nuclear Envelope - ultrastructure Phagocytosis Protein Domains Receptors, Cytoplasmic and Nuclear - chemistry Receptors, Cytoplasmic and Nuclear - metabolism Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae - ultrastructure Saccharomyces cerevisiae Proteins - chemistry Saccharomyces cerevisiae Proteins - metabolism Structure-Activity Relationship Time Factors Vacuoles - metabolism Vacuoles - ultrastructure Vesicles Vesicular Transport Proteins - metabolism |
| title | Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome |
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