Chemical-Genetic Inhibition of a Sensitized Mutant Myosin Vb Demonstrates a Role in Peripheral-Pericentriolar Membrane Traffic
Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N6-substituted ADP analog that inhibits...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2004-02, Vol.101 (7), p.1868-1873 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1873 |
|---|---|
| container_issue | 7 |
| container_start_page | 1868 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 101 |
| creator | Provance, D. William Gourley, Christopher R. Silan, Colleen M. Cameron, L. C. Shokat, Kevan M. Goldenring, James R. Shah, Kavita Gillespie, Peter G. Mercer, John A. Spudich, James A. |
| description | Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N6-substituted ADP analog that inhibits its activity, causing it to remain tightly bound to actin. Inhibition of the sensitized mutant causes inhibition of accumulation of transferrin in the cytoplasm and increases levels of plasma-membrane transferrin receptor, suggesting that myosin Vb functions in traffic between peripheral and pericentrosomal compartments. |
| doi_str_mv | 10.1073/pnas.0305895101 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_19254088</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>3371362</jstor_id><sourcerecordid>3371362</sourcerecordid><originalsourceid>FETCH-LOGICAL-c522t-10d6ffb2c6f9a0df010779bda3812c1f568e5b30dee5006c053818e21f3e048b3</originalsourceid><addsrcrecordid>eNqFkkFv1DAQhSMEokvhzAUhiwOc0o7jxHEOPaAF2kpdFUHhajnJmPUqsRfbQZQDvx1vd9UtqBIn25rvPc0bT5Y9p3BEoWbHa6vCETCoRFNRoA-yGYWG5rxs4GE2AyjqXJRFeZA9CWEFAE0l4HF2QMua80awWfZ7vsTRdGrIT9FiNB05t0vTmmicJU4TRT6jDen5C3uymKKykSyuXTCWfG3JOxydDdGriCGhn9yAJFU-ojfrJfrkurl2aKM3blCeLHBsvbJIrrzS2nRPs0daDQGf7c7D7MuH91fzs_zi8vR8_vYi76qiiDmFnmvdFh3XjYJeQwpfN22vmKBFR3XFBVYtgx6xAuAdVKkgsKCaIZSiZYfZydZ3PbUj9jcdqUGuvRmVv5ZOGfl3xZql_OZ-SFbVQJukf73Te_d9whDlaEKHw5CyuClIAZQLTuv_grQpqhKESOCrf8CVm7xNQ5AF0JKmCJCg4y3UeReCR33bMQW5WQC5WQC5X4CkeHk36J7f_XgC3uyAjXJvR2UtqeBC6mkYIv6Md6zuJxPwYgusQnT-lmCspowX7A9xts8x</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201410530</pqid></control><display><type>article</type><title>Chemical-Genetic Inhibition of a Sensitized Mutant Myosin Vb Demonstrates a Role in Peripheral-Pericentriolar Membrane Traffic</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Provance, D. William ; Gourley, Christopher R. ; Silan, Colleen M. ; Cameron, L. C. ; Shokat, Kevan M. ; Goldenring, James R. ; Shah, Kavita ; Gillespie, Peter G. ; Mercer, John A. ; Spudich, James A.</creator><creatorcontrib>Provance, D. William ; Gourley, Christopher R. ; Silan, Colleen M. ; Cameron, L. C. ; Shokat, Kevan M. ; Goldenring, James R. ; Shah, Kavita ; Gillespie, Peter G. ; Mercer, John A. ; Spudich, James A.</creatorcontrib><description>Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N6-substituted ADP analog that inhibits its activity, causing it to remain tightly bound to actin. Inhibition of the sensitized mutant causes inhibition of accumulation of transferrin in the cytoplasm and increases levels of plasma-membrane transferrin receptor, suggesting that myosin Vb functions in traffic between peripheral and pericentrosomal compartments.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0305895101</identifier><identifier>PMID: 14766983</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Actins ; Actins - metabolism ; Adenosine Diphosphate - metabolism ; Adenosine Triphosphate - metabolism ; ADP ; Amino Acid Sequence ; Animals ; Biological Sciences ; Cell lines ; Cell Membrane - metabolism ; Cell membranes ; Cellular biology ; Centrioles - metabolism ; Chemicals ; Fluorescence ; Genetics ; HeLa Cells ; Humans ; Membranes ; Models, Biological ; Molecular Sequence Data ; Motor ability ; Mutation ; Myosin Type V - antagonists & inhibitors ; Myosin Type V - genetics ; Myosin Type V - metabolism ; Protein Engineering ; Protein Transport ; Rats ; Receptors ; Receptors, Transferrin - metabolism ; Recycling ; Transferrin - metabolism ; Transferrin receptors ; Transferrins</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2004-02, Vol.101 (7), p.1868-1873</ispartof><rights>Copyright 1993/2004 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 17, 2004</rights><rights>Copyright © 2004, The National Academy of Sciences 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-10d6ffb2c6f9a0df010779bda3812c1f568e5b30dee5006c053818e21f3e048b3</citedby><cites>FETCH-LOGICAL-c522t-10d6ffb2c6f9a0df010779bda3812c1f568e5b30dee5006c053818e21f3e048b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/101/7.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3371362$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3371362$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14766983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Provance, D. William</creatorcontrib><creatorcontrib>Gourley, Christopher R.</creatorcontrib><creatorcontrib>Silan, Colleen M.</creatorcontrib><creatorcontrib>Cameron, L. C.</creatorcontrib><creatorcontrib>Shokat, Kevan M.</creatorcontrib><creatorcontrib>Goldenring, James R.</creatorcontrib><creatorcontrib>Shah, Kavita</creatorcontrib><creatorcontrib>Gillespie, Peter G.</creatorcontrib><creatorcontrib>Mercer, John A.</creatorcontrib><creatorcontrib>Spudich, James A.</creatorcontrib><title>Chemical-Genetic Inhibition of a Sensitized Mutant Myosin Vb Demonstrates a Role in Peripheral-Pericentriolar Membrane Traffic</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N6-substituted ADP analog that inhibits its activity, causing it to remain tightly bound to actin. Inhibition of the sensitized mutant causes inhibition of accumulation of transferrin in the cytoplasm and increases levels of plasma-membrane transferrin receptor, suggesting that myosin Vb functions in traffic between peripheral and pericentrosomal compartments.</description><subject>Actins</subject><subject>Actins - metabolism</subject><subject>Adenosine Diphosphate - metabolism</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>ADP</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cell lines</subject><subject>Cell Membrane - metabolism</subject><subject>Cell membranes</subject><subject>Cellular biology</subject><subject>Centrioles - metabolism</subject><subject>Chemicals</subject><subject>Fluorescence</subject><subject>Genetics</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Membranes</subject><subject>Models, Biological</subject><subject>Molecular Sequence Data</subject><subject>Motor ability</subject><subject>Mutation</subject><subject>Myosin Type V - antagonists & inhibitors</subject><subject>Myosin Type V - genetics</subject><subject>Myosin Type V - metabolism</subject><subject>Protein Engineering</subject><subject>Protein Transport</subject><subject>Rats</subject><subject>Receptors</subject><subject>Receptors, Transferrin - metabolism</subject><subject>Recycling</subject><subject>Transferrin - metabolism</subject><subject>Transferrin receptors</subject><subject>Transferrins</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkkFv1DAQhSMEokvhzAUhiwOc0o7jxHEOPaAF2kpdFUHhajnJmPUqsRfbQZQDvx1vd9UtqBIn25rvPc0bT5Y9p3BEoWbHa6vCETCoRFNRoA-yGYWG5rxs4GE2AyjqXJRFeZA9CWEFAE0l4HF2QMua80awWfZ7vsTRdGrIT9FiNB05t0vTmmicJU4TRT6jDen5C3uymKKykSyuXTCWfG3JOxydDdGriCGhn9yAJFU-ojfrJfrkurl2aKM3blCeLHBsvbJIrrzS2nRPs0daDQGf7c7D7MuH91fzs_zi8vR8_vYi76qiiDmFnmvdFh3XjYJeQwpfN22vmKBFR3XFBVYtgx6xAuAdVKkgsKCaIZSiZYfZydZ3PbUj9jcdqUGuvRmVv5ZOGfl3xZql_OZ-SFbVQJukf73Te_d9whDlaEKHw5CyuClIAZQLTuv_grQpqhKESOCrf8CVm7xNQ5AF0JKmCJCg4y3UeReCR33bMQW5WQC5WQC5X4CkeHk36J7f_XgC3uyAjXJvR2UtqeBC6mkYIv6Md6zuJxPwYgusQnT-lmCspowX7A9xts8x</recordid><startdate>20040217</startdate><enddate>20040217</enddate><creator>Provance, D. William</creator><creator>Gourley, Christopher R.</creator><creator>Silan, Colleen M.</creator><creator>Cameron, L. C.</creator><creator>Shokat, Kevan M.</creator><creator>Goldenring, James R.</creator><creator>Shah, Kavita</creator><creator>Gillespie, Peter G.</creator><creator>Mercer, John A.</creator><creator>Spudich, James A.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</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></search><sort><creationdate>20040217</creationdate><title>Chemical-Genetic Inhibition of a Sensitized Mutant Myosin Vb Demonstrates a Role in Peripheral-Pericentriolar Membrane Traffic</title><author>Provance, D. William ; Gourley, Christopher R. ; Silan, Colleen M. ; Cameron, L. C. ; Shokat, Kevan M. ; Goldenring, James R. ; Shah, Kavita ; Gillespie, Peter G. ; Mercer, John A. ; Spudich, James A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-10d6ffb2c6f9a0df010779bda3812c1f568e5b30dee5006c053818e21f3e048b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Actins</topic><topic>Actins - metabolism</topic><topic>Adenosine Diphosphate - metabolism</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>ADP</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>Cell lines</topic><topic>Cell Membrane - metabolism</topic><topic>Cell membranes</topic><topic>Cellular biology</topic><topic>Centrioles - metabolism</topic><topic>Chemicals</topic><topic>Fluorescence</topic><topic>Genetics</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Membranes</topic><topic>Models, Biological</topic><topic>Molecular Sequence Data</topic><topic>Motor ability</topic><topic>Mutation</topic><topic>Myosin Type V - antagonists & inhibitors</topic><topic>Myosin Type V - genetics</topic><topic>Myosin Type V - metabolism</topic><topic>Protein Engineering</topic><topic>Protein Transport</topic><topic>Rats</topic><topic>Receptors</topic><topic>Receptors, Transferrin - metabolism</topic><topic>Recycling</topic><topic>Transferrin - metabolism</topic><topic>Transferrin receptors</topic><topic>Transferrins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Provance, D. William</creatorcontrib><creatorcontrib>Gourley, Christopher R.</creatorcontrib><creatorcontrib>Silan, Colleen M.</creatorcontrib><creatorcontrib>Cameron, L. C.</creatorcontrib><creatorcontrib>Shokat, Kevan M.</creatorcontrib><creatorcontrib>Goldenring, James R.</creatorcontrib><creatorcontrib>Shah, Kavita</creatorcontrib><creatorcontrib>Gillespie, Peter G.</creatorcontrib><creatorcontrib>Mercer, John A.</creatorcontrib><creatorcontrib>Spudich, James A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Provance, D. William</au><au>Gourley, Christopher R.</au><au>Silan, Colleen M.</au><au>Cameron, L. C.</au><au>Shokat, Kevan M.</au><au>Goldenring, James R.</au><au>Shah, Kavita</au><au>Gillespie, Peter G.</au><au>Mercer, John A.</au><au>Spudich, James A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemical-Genetic Inhibition of a Sensitized Mutant Myosin Vb Demonstrates a Role in Peripheral-Pericentriolar Membrane Traffic</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2004-02-17</date><risdate>2004</risdate><volume>101</volume><issue>7</issue><spage>1868</spage><epage>1873</epage><pages>1868-1873</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N6-substituted ADP analog that inhibits its activity, causing it to remain tightly bound to actin. Inhibition of the sensitized mutant causes inhibition of accumulation of transferrin in the cytoplasm and increases levels of plasma-membrane transferrin receptor, suggesting that myosin Vb functions in traffic between peripheral and pericentrosomal compartments.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>14766983</pmid><doi>10.1073/pnas.0305895101</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2004-02, Vol.101 (7), p.1868-1873 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_19254088 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Actins Actins - metabolism Adenosine Diphosphate - metabolism Adenosine Triphosphate - metabolism ADP Amino Acid Sequence Animals Biological Sciences Cell lines Cell Membrane - metabolism Cell membranes Cellular biology Centrioles - metabolism Chemicals Fluorescence Genetics HeLa Cells Humans Membranes Models, Biological Molecular Sequence Data Motor ability Mutation Myosin Type V - antagonists & inhibitors Myosin Type V - genetics Myosin Type V - metabolism Protein Engineering Protein Transport Rats Receptors Receptors, Transferrin - metabolism Recycling Transferrin - metabolism Transferrin receptors Transferrins |
| title | Chemical-Genetic Inhibition of a Sensitized Mutant Myosin Vb Demonstrates a Role in Peripheral-Pericentriolar Membrane Traffic |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T14%3A31%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chemical-Genetic%20Inhibition%20of%20a%20Sensitized%20Mutant%20Myosin%20Vb%20Demonstrates%20a%20Role%20in%20Peripheral-Pericentriolar%20Membrane%20Traffic&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Provance,%20D.%20William&rft.date=2004-02-17&rft.volume=101&rft.issue=7&rft.spage=1868&rft.epage=1873&rft.pages=1868-1873&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.0305895101&rft_dat=%3Cjstor_proqu%3E3371362%3C/jstor_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201410530&rft_id=info:pmid/14766983&rft_jstor_id=3371362&rfr_iscdi=true |