V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway
The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subun...
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| Veröffentlicht in: | Nature cell biology 2006-02, Vol.8 (2), p.124-136 |
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| creator | Marshansky, Vladimir Hurtado-Lorenzo, Andrés Skinner, Mhairi Annan, Jaafar El Futai, Masamitsu Sun-Wada, Ge-Hong Bourgoin, Sylvain Casanova, James Wildeman, Alan Bechoua, Shaliha Ausiello, Dennis A Brown, Dennis |
| description | The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery. |
| doi_str_mv | 10.1038/ncb1348 |
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The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb1348</identifier><identifier>PMID: 16415858</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Acidification ; Adenosine triphosphatase ; ADP-Ribosylation Factors - metabolism ; Ammonium Chloride - pharmacology ; Animals ; Biodegradation ; Biology ; Biomedical and Life Sciences ; Cancer Research ; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology ; Cell Biology ; Cell Line ; Cellular control mechanisms ; Developmental Biology ; Dynamins - genetics ; Dynamins - metabolism ; Endocytosis - drug effects ; Endocytosis - physiology ; Endosomes - drug effects ; Endosomes - metabolism ; Epithelial Cells - metabolism ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; GTPase-Activating Proteins - genetics ; GTPase-Activating Proteins - metabolism ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration - drug effects ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Kidney Tubules, Proximal - cytology ; Kidney Tubules, Proximal - metabolism ; Life Sciences ; Macrolides - pharmacology ; Membranes ; Mice ; Models, Biological ; Mutation - genetics ; Physiological aspects ; Protein Binding ; Protein Interaction Mapping ; Protein Transport - physiology ; Proteins ; Proteins - metabolism ; Protons ; Serum Albumin, Bovine - metabolism ; Stem Cells ; Transfection ; Vacuolar Proton-Translocating ATPases - antagonists & inhibitors ; Vacuolar Proton-Translocating ATPases - genetics ; Vacuolar Proton-Translocating ATPases - metabolism ; Vacuoles</subject><ispartof>Nature cell biology, 2006-02, Vol.8 (2), p.124-136</ispartof><rights>Springer Nature Limited 2006</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-c7eb0a73c0cb34dcabb8bdc54771ff5cb1893b21f954ad1ff8da7a7c882b059b3</citedby><cites>FETCH-LOGICAL-c434t-c7eb0a73c0cb34dcabb8bdc54771ff5cb1893b21f954ad1ff8da7a7c882b059b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncb1348$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ncb1348$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16415858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marshansky, Vladimir</creatorcontrib><creatorcontrib>Hurtado-Lorenzo, Andrés</creatorcontrib><creatorcontrib>Skinner, Mhairi</creatorcontrib><creatorcontrib>Annan, Jaafar El</creatorcontrib><creatorcontrib>Futai, Masamitsu</creatorcontrib><creatorcontrib>Sun-Wada, Ge-Hong</creatorcontrib><creatorcontrib>Bourgoin, Sylvain</creatorcontrib><creatorcontrib>Casanova, James</creatorcontrib><creatorcontrib>Wildeman, Alan</creatorcontrib><creatorcontrib>Bechoua, Shaliha</creatorcontrib><creatorcontrib>Ausiello, Dennis A</creatorcontrib><creatorcontrib>Brown, Dennis</creatorcontrib><title>V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. 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metabolism</topic><topic>Ammonium Chloride - pharmacology</topic><topic>Animals</topic><topic>Biodegradation</topic><topic>Biology</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer Research</topic><topic>Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology</topic><topic>Cell Biology</topic><topic>Cell Line</topic><topic>Cellular control mechanisms</topic><topic>Developmental Biology</topic><topic>Dynamins - genetics</topic><topic>Dynamins - metabolism</topic><topic>Endocytosis - drug effects</topic><topic>Endocytosis - physiology</topic><topic>Endosomes - drug effects</topic><topic>Endosomes - metabolism</topic><topic>Epithelial Cells - metabolism</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>GTPase-Activating Proteins - genetics</topic><topic>GTPase-Activating Proteins - metabolism</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration - drug effects</topic><topic>Isoenzymes - 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Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marshansky, Vladimir</au><au>Hurtado-Lorenzo, Andrés</au><au>Skinner, Mhairi</au><au>Annan, Jaafar El</au><au>Futai, Masamitsu</au><au>Sun-Wada, Ge-Hong</au><au>Bourgoin, Sylvain</au><au>Casanova, James</au><au>Wildeman, Alan</au><au>Bechoua, Shaliha</au><au>Ausiello, Dennis A</au><au>Brown, Dennis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2006-02-01</date><risdate>2006</risdate><volume>8</volume><issue>2</issue><spage>124</spage><epage>136</epage><pages>124-136</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16415858</pmid><doi>10.1038/ncb1348</doi><tpages>13</tpages></addata></record> |
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| subjects | Acidification Adenosine triphosphatase ADP-Ribosylation Factors - metabolism Ammonium Chloride - pharmacology Animals Biodegradation Biology Biomedical and Life Sciences Cancer Research Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology Cell Biology Cell Line Cellular control mechanisms Developmental Biology Dynamins - genetics Dynamins - metabolism Endocytosis - drug effects Endocytosis - physiology Endosomes - drug effects Endosomes - metabolism Epithelial Cells - metabolism Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism GTPase-Activating Proteins - genetics GTPase-Activating Proteins - metabolism HeLa Cells Humans Hydrogen-Ion Concentration - drug effects Isoenzymes - genetics Isoenzymes - metabolism Kidney Tubules, Proximal - cytology Kidney Tubules, Proximal - metabolism Life Sciences Macrolides - pharmacology Membranes Mice Models, Biological Mutation - genetics Physiological aspects Protein Binding Protein Interaction Mapping Protein Transport - physiology Proteins Proteins - metabolism Protons Serum Albumin, Bovine - metabolism Stem Cells Transfection Vacuolar Proton-Translocating ATPases - antagonists & inhibitors Vacuolar Proton-Translocating ATPases - genetics Vacuolar Proton-Translocating ATPases - metabolism Vacuoles |
| title | V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway |
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