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Nuclear aggresomes form by fusion of PML-associated aggregates
Nuclear aggregates formed by proteins containing expanded poly-glutamine (poly-Q) tracts have been linked to the pathogenesis of poly-Q neurodegenerative diseases. Here, we show that a protein (GFP170*) lacking poly-Q tracts forms nuclear aggregates that share characteristics of poly-Q aggregates. G...
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Published in: | Molecular biology of the cell 2005-10, Vol.16 (10), p.4905-4917 |
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creator | Fu, Lianwu Gao, Ya-Sheng Tousson, Albert Shah, Anish Chen, Tung-Ling L Vertel, Barbara M Sztul, Elizabeth |
description | Nuclear aggregates formed by proteins containing expanded poly-glutamine (poly-Q) tracts have been linked to the pathogenesis of poly-Q neurodegenerative diseases. Here, we show that a protein (GFP170*) lacking poly-Q tracts forms nuclear aggregates that share characteristics of poly-Q aggregates. GFP170* aggregates recruit cellular chaperones and proteasomes, and alter the organization of nuclear domains containing the promyelocytic leukemia (PML) protein. These results suggest that the formation of nuclear aggregates and their effects on nuclear architecture are not specific to poly-Q proteins. Using GFP170* as a model substrate, we explored the mechanistic details of nuclear aggregate formation. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching analyses show that GFP170* molecules exchange rapidly between aggregates and a soluble pool of GFP170*, indicating that the aggregates are dynamic accumulations of GFP170*. The formation of cytoplasmic and nuclear GFP170* aggregates is microtubule-dependent. We show that within the nucleus, GFP170* initially deposits in small aggregates at or adjacent to PML bodies. Time-lapse imaging of live cells shows that small aggregates move toward each other and fuse to form larger aggregates. The coalescence of the aggregates is accompanied by spatial rearrangements of the PML bodies. Significantly, we find that the larger nuclear aggregates have complex internal substructures that reposition extensively during fusion of the aggregates. These studies suggest that nuclear aggregates may be viewed as dynamic multidomain inclusions that continuously remodel their components. |
doi_str_mv | 10.1091/mbc.E05-01-0019 |
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Here, we show that a protein (GFP170*) lacking poly-Q tracts forms nuclear aggregates that share characteristics of poly-Q aggregates. GFP170* aggregates recruit cellular chaperones and proteasomes, and alter the organization of nuclear domains containing the promyelocytic leukemia (PML) protein. These results suggest that the formation of nuclear aggregates and their effects on nuclear architecture are not specific to poly-Q proteins. Using GFP170* as a model substrate, we explored the mechanistic details of nuclear aggregate formation. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching analyses show that GFP170* molecules exchange rapidly between aggregates and a soluble pool of GFP170*, indicating that the aggregates are dynamic accumulations of GFP170*. The formation of cytoplasmic and nuclear GFP170* aggregates is microtubule-dependent. We show that within the nucleus, GFP170* initially deposits in small aggregates at or adjacent to PML bodies. Time-lapse imaging of live cells shows that small aggregates move toward each other and fuse to form larger aggregates. The coalescence of the aggregates is accompanied by spatial rearrangements of the PML bodies. Significantly, we find that the larger nuclear aggregates have complex internal substructures that reposition extensively during fusion of the aggregates. These studies suggest that nuclear aggregates may be viewed as dynamic multidomain inclusions that continuously remodel their components.</description><identifier>ISSN: 1059-1524</identifier><identifier>EISSN: 1939-4586</identifier><identifier>EISSN: 1059-1524</identifier><identifier>DOI: 10.1091/mbc.E05-01-0019</identifier><identifier>PMID: 16055507</identifier><language>eng</language><publisher>United States</publisher><subject>Aggrecans ; Animals ; Cell Nucleus - metabolism ; Cell Nucleus - ultrastructure ; Chlorocebus aethiops ; COS Cells ; Cytoplasm - metabolism ; Cytoplasm - ultrastructure ; Extracellular Matrix Proteins - metabolism ; Green Fluorescent Proteins - genetics ; Lectins, C-Type - metabolism ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Microscopy, Electron, Transmission ; Nuclear Proteins - metabolism ; Peptides - genetics ; Proteasome Endopeptidase Complex - metabolism ; Protein Folding ; Protein Transport ; Proteoglycans - metabolism ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Molecular biology of the cell, 2005-10, Vol.16 (10), p.4905-4917</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-962405a116c8bd1f76383aa01057932385e90f79288e3c82966d295adb4b79a03</citedby><cites>FETCH-LOGICAL-c511t-962405a116c8bd1f76383aa01057932385e90f79288e3c82966d295adb4b79a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16055507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fu, Lianwu</creatorcontrib><creatorcontrib>Gao, Ya-Sheng</creatorcontrib><creatorcontrib>Tousson, Albert</creatorcontrib><creatorcontrib>Shah, Anish</creatorcontrib><creatorcontrib>Chen, Tung-Ling L</creatorcontrib><creatorcontrib>Vertel, Barbara M</creatorcontrib><creatorcontrib>Sztul, Elizabeth</creatorcontrib><title>Nuclear aggresomes form by fusion of PML-associated aggregates</title><title>Molecular biology of the cell</title><addtitle>Mol Biol Cell</addtitle><description>Nuclear aggregates formed by proteins containing expanded poly-glutamine (poly-Q) tracts have been linked to the pathogenesis of poly-Q neurodegenerative diseases. Here, we show that a protein (GFP170*) lacking poly-Q tracts forms nuclear aggregates that share characteristics of poly-Q aggregates. GFP170* aggregates recruit cellular chaperones and proteasomes, and alter the organization of nuclear domains containing the promyelocytic leukemia (PML) protein. These results suggest that the formation of nuclear aggregates and their effects on nuclear architecture are not specific to poly-Q proteins. Using GFP170* as a model substrate, we explored the mechanistic details of nuclear aggregate formation. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching analyses show that GFP170* molecules exchange rapidly between aggregates and a soluble pool of GFP170*, indicating that the aggregates are dynamic accumulations of GFP170*. The formation of cytoplasmic and nuclear GFP170* aggregates is microtubule-dependent. We show that within the nucleus, GFP170* initially deposits in small aggregates at or adjacent to PML bodies. Time-lapse imaging of live cells shows that small aggregates move toward each other and fuse to form larger aggregates. The coalescence of the aggregates is accompanied by spatial rearrangements of the PML bodies. Significantly, we find that the larger nuclear aggregates have complex internal substructures that reposition extensively during fusion of the aggregates. These studies suggest that nuclear aggregates may be viewed as dynamic multidomain inclusions that continuously remodel their components.</description><subject>Aggrecans</subject><subject>Animals</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Nucleus - ultrastructure</subject><subject>Chlorocebus aethiops</subject><subject>COS Cells</subject><subject>Cytoplasm - metabolism</subject><subject>Cytoplasm - ultrastructure</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Lectins, C-Type - metabolism</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Microscopy, Electron, Transmission</subject><subject>Nuclear Proteins - metabolism</subject><subject>Peptides - genetics</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Protein Folding</subject><subject>Protein Transport</subject><subject>Proteoglycans - metabolism</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>1059-1524</issn><issn>1939-4586</issn><issn>1059-1524</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkDtPwzAUhS0EoqUws6FMbG7vjR-xFySEykMqjwFmy3Gcqiipi90M_fe4aiVGpnuG7x4dfYRcI0wRNM762k3nICggBUB9QsaomaZcKHmaMwhNUZR8RC5S-s4E57I6JyOUIISAakzu3gbXeRsLu1xGn0LvU9GG2Bf1rmiHtArrIrTFx-uC2pSCW9mtbw7sMsd0Sc5a2yV_dbwT8vU4_3x4pov3p5eH-wV1AnFLtSw5CIsonaobbCvJFLMW8sBKs5Ip4TW0lS6V8sypUkvZlFrYpuZ1pS2wCbk99G5i-Bl82pp-lZzvOrv2YUhGqtzIefkviHmKVrrK4OwAuhhSir41m7jqbdwZBLN3a7Jb40EYQLN3mz9ujtVD3fvmjz_KZL91rHMV</recordid><startdate>200510</startdate><enddate>200510</enddate><creator>Fu, Lianwu</creator><creator>Gao, Ya-Sheng</creator><creator>Tousson, Albert</creator><creator>Shah, Anish</creator><creator>Chen, Tung-Ling L</creator><creator>Vertel, Barbara M</creator><creator>Sztul, Elizabeth</creator><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>7TK</scope><scope>7X8</scope></search><sort><creationdate>200510</creationdate><title>Nuclear aggresomes form by fusion of PML-associated aggregates</title><author>Fu, Lianwu ; Gao, Ya-Sheng ; Tousson, Albert ; Shah, Anish ; Chen, Tung-Ling L ; Vertel, Barbara M ; Sztul, Elizabeth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-962405a116c8bd1f76383aa01057932385e90f79288e3c82966d295adb4b79a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Aggrecans</topic><topic>Animals</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Nucleus - ultrastructure</topic><topic>Chlorocebus aethiops</topic><topic>COS Cells</topic><topic>Cytoplasm - metabolism</topic><topic>Cytoplasm - ultrastructure</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Lectins, C-Type - metabolism</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Microscopy, Electron, Transmission</topic><topic>Nuclear Proteins - metabolism</topic><topic>Peptides - genetics</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Protein Folding</topic><topic>Protein Transport</topic><topic>Proteoglycans - metabolism</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fu, Lianwu</creatorcontrib><creatorcontrib>Gao, Ya-Sheng</creatorcontrib><creatorcontrib>Tousson, Albert</creatorcontrib><creatorcontrib>Shah, Anish</creatorcontrib><creatorcontrib>Chen, Tung-Ling L</creatorcontrib><creatorcontrib>Vertel, Barbara M</creatorcontrib><creatorcontrib>Sztul, Elizabeth</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fu, Lianwu</au><au>Gao, Ya-Sheng</au><au>Tousson, Albert</au><au>Shah, Anish</au><au>Chen, Tung-Ling L</au><au>Vertel, Barbara M</au><au>Sztul, Elizabeth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nuclear aggresomes form by fusion of PML-associated aggregates</atitle><jtitle>Molecular biology of the cell</jtitle><addtitle>Mol Biol Cell</addtitle><date>2005-10</date><risdate>2005</risdate><volume>16</volume><issue>10</issue><spage>4905</spage><epage>4917</epage><pages>4905-4917</pages><issn>1059-1524</issn><eissn>1939-4586</eissn><eissn>1059-1524</eissn><abstract>Nuclear aggregates formed by proteins containing expanded poly-glutamine (poly-Q) tracts have been linked to the pathogenesis of poly-Q neurodegenerative diseases. Here, we show that a protein (GFP170*) lacking poly-Q tracts forms nuclear aggregates that share characteristics of poly-Q aggregates. GFP170* aggregates recruit cellular chaperones and proteasomes, and alter the organization of nuclear domains containing the promyelocytic leukemia (PML) protein. These results suggest that the formation of nuclear aggregates and their effects on nuclear architecture are not specific to poly-Q proteins. Using GFP170* as a model substrate, we explored the mechanistic details of nuclear aggregate formation. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching analyses show that GFP170* molecules exchange rapidly between aggregates and a soluble pool of GFP170*, indicating that the aggregates are dynamic accumulations of GFP170*. The formation of cytoplasmic and nuclear GFP170* aggregates is microtubule-dependent. We show that within the nucleus, GFP170* initially deposits in small aggregates at or adjacent to PML bodies. Time-lapse imaging of live cells shows that small aggregates move toward each other and fuse to form larger aggregates. The coalescence of the aggregates is accompanied by spatial rearrangements of the PML bodies. Significantly, we find that the larger nuclear aggregates have complex internal substructures that reposition extensively during fusion of the aggregates. These studies suggest that nuclear aggregates may be viewed as dynamic multidomain inclusions that continuously remodel their components.</abstract><cop>United States</cop><pmid>16055507</pmid><doi>10.1091/mbc.E05-01-0019</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aggrecans Animals Cell Nucleus - metabolism Cell Nucleus - ultrastructure Chlorocebus aethiops COS Cells Cytoplasm - metabolism Cytoplasm - ultrastructure Extracellular Matrix Proteins - metabolism Green Fluorescent Proteins - genetics Lectins, C-Type - metabolism Membrane Proteins - genetics Membrane Proteins - metabolism Microscopy, Electron, Transmission Nuclear Proteins - metabolism Peptides - genetics Proteasome Endopeptidase Complex - metabolism Protein Folding Protein Transport Proteoglycans - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Tumor Suppressor Proteins - metabolism |
title | Nuclear aggresomes form by fusion of PML-associated aggregates |
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