mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1
Lissencephaly is a devastating neurological disorder caused by defective neuronal migration. The LIS1 (or PAFAH1B1 ) gene was identified as the gene mutated in lissencephaly patients, and was found to regulate cytoplasmic dynein function and localization. In particular, LIS1 is essential for anterog...
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| Veröffentlicht in: | The EMBO journal 2010-02, Vol.29 (3), p.517-531 |
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| creator | Yamada, Masami Toba, Shiori Takitoh, Takako Yoshida, Yuko Mori, Daisuke Nakamura, Takeshi Iwane, Atsuko H Yanagida, Toshio Imai, Hiroshi Yu-Lee, Li-yuan Schroer, Trina Wynshaw-Boris, Anthony Hirotsune, Shinji |
| description | Lissencephaly is a devastating neurological disorder caused by defective neuronal migration. The
LIS1
(or
PAFAH1B1
) gene was identified as the gene mutated in lissencephaly patients, and was found to regulate cytoplasmic dynein function and localization. In particular, LIS1 is essential for anterograde transport of cytoplasmic dynein as a part of the cytoplasmic dynein–LIS1–microtubule complex in a kinesin‐1‐dependent manner. However, the underlying mechanism by which a cytoplasmic dynein–LIS1–microtubule complex binds kinesin‐1 is unknown. Here, we report that mNUDC (mammalian NUDC) interacts with kinesin‐1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin‐1. mNUDC is also required for anterograde transport of a dynactin‐containing complex. Inhibition of mNUDC severely suppressed anterograde transport of distinct cytoplasmic dynein and dynactin complexes, whereas motility of kinesin‐1 remained intact. Reconstruction experiments clearly demonstrated that mNUDC mediates the interaction of the dynein or dynactin complex with kinesin‐1 and supports their transport by kinesin‐1. Our findings have uncovered an essential role of mNUDC for anterograde transport of dynein and dynactin by kinesin‐1. |
| doi_str_mv | 10.1038/emboj.2009.378 |
| format | Article |
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LIS1
(or
PAFAH1B1
) gene was identified as the gene mutated in lissencephaly patients, and was found to regulate cytoplasmic dynein function and localization. In particular, LIS1 is essential for anterograde transport of cytoplasmic dynein as a part of the cytoplasmic dynein–LIS1–microtubule complex in a kinesin‐1‐dependent manner. However, the underlying mechanism by which a cytoplasmic dynein–LIS1–microtubule complex binds kinesin‐1 is unknown. Here, we report that mNUDC (mammalian NUDC) interacts with kinesin‐1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin‐1. mNUDC is also required for anterograde transport of a dynactin‐containing complex. Inhibition of mNUDC severely suppressed anterograde transport of distinct cytoplasmic dynein and dynactin complexes, whereas motility of kinesin‐1 remained intact. Reconstruction experiments clearly demonstrated that mNUDC mediates the interaction of the dynein or dynactin complex with kinesin‐1 and supports their transport by kinesin‐1. Our findings have uncovered an essential role of mNUDC for anterograde transport of dynein and dynactin by kinesin‐1.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2009.378</identifier><identifier>PMID: 20019668</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>adaptor ; Animals ; Biological Transport - drug effects ; Biological Transport - physiology ; Cell Cycle Proteins - antagonists & inhibitors ; Cell Cycle Proteins - metabolism ; Cell Cycle Proteins - physiology ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cells, Cultured ; Cytoplasm - metabolism ; Cytoplasmic Dyneins - metabolism ; Dynactin Complex ; dynein ; EMBO20 ; Ganglia, Spinal - metabolism ; Kinesin - metabolism ; Kinesin - physiology ; kinesin-1 ; Lis1 ; Mammals ; Mice ; Microtubule-Associated Proteins - metabolism ; mNUDC ; Models, Biological ; Neurons - drug effects ; Neurons - metabolism ; Nuclear Proteins - antagonists & inhibitors ; Nuclear Proteins - metabolism ; Nuclear Proteins - physiology ; Protein Binding - drug effects ; RNA, Small Interfering - pharmacology ; Swine</subject><ispartof>The EMBO journal, 2010-02, Vol.29 (3), p.517-531</ispartof><rights>European Molecular Biology Organization 2010</rights><rights>Copyright © 2010 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Feb 3, 2010</rights><rights>Copyright © 2010, European Molecular Biology Organization 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5768-9ec692c3d325d0b932677b4802b9d1f02648492d75a1ef467d4fa1f4307280fe3</citedby><cites>FETCH-LOGICAL-c5768-9ec692c3d325d0b932677b4802b9d1f02648492d75a1ef467d4fa1f4307280fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830693/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830693/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,41096,42165,45550,45551,46384,46808,51551,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/emboj.2009.378$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20019668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Masami</creatorcontrib><creatorcontrib>Toba, Shiori</creatorcontrib><creatorcontrib>Takitoh, Takako</creatorcontrib><creatorcontrib>Yoshida, Yuko</creatorcontrib><creatorcontrib>Mori, Daisuke</creatorcontrib><creatorcontrib>Nakamura, Takeshi</creatorcontrib><creatorcontrib>Iwane, Atsuko H</creatorcontrib><creatorcontrib>Yanagida, Toshio</creatorcontrib><creatorcontrib>Imai, Hiroshi</creatorcontrib><creatorcontrib>Yu-Lee, Li-yuan</creatorcontrib><creatorcontrib>Schroer, Trina</creatorcontrib><creatorcontrib>Wynshaw-Boris, Anthony</creatorcontrib><creatorcontrib>Hirotsune, Shinji</creatorcontrib><title>mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Lissencephaly is a devastating neurological disorder caused by defective neuronal migration. The
LIS1
(or
PAFAH1B1
) gene was identified as the gene mutated in lissencephaly patients, and was found to regulate cytoplasmic dynein function and localization. In particular, LIS1 is essential for anterograde transport of cytoplasmic dynein as a part of the cytoplasmic dynein–LIS1–microtubule complex in a kinesin‐1‐dependent manner. However, the underlying mechanism by which a cytoplasmic dynein–LIS1–microtubule complex binds kinesin‐1 is unknown. Here, we report that mNUDC (mammalian NUDC) interacts with kinesin‐1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin‐1. mNUDC is also required for anterograde transport of a dynactin‐containing complex. Inhibition of mNUDC severely suppressed anterograde transport of distinct cytoplasmic dynein and dynactin complexes, whereas motility of kinesin‐1 remained intact. Reconstruction experiments clearly demonstrated that mNUDC mediates the interaction of the dynein or dynactin complex with kinesin‐1 and supports their transport by kinesin‐1. Our findings have uncovered an essential role of mNUDC for anterograde transport of dynein and dynactin by kinesin‐1.</description><subject>adaptor</subject><subject>Animals</subject><subject>Biological Transport - drug effects</subject><subject>Biological Transport - physiology</subject><subject>Cell Cycle Proteins - antagonists & inhibitors</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Cycle Proteins - physiology</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Cytoplasm - metabolism</subject><subject>Cytoplasmic Dyneins - metabolism</subject><subject>Dynactin Complex</subject><subject>dynein</subject><subject>EMBO20</subject><subject>Ganglia, Spinal - metabolism</subject><subject>Kinesin - metabolism</subject><subject>Kinesin - physiology</subject><subject>kinesin-1</subject><subject>Lis1</subject><subject>Mammals</subject><subject>Mice</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>mNUDC</subject><subject>Models, Biological</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Nuclear Proteins - antagonists & inhibitors</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nuclear Proteins - physiology</subject><subject>Protein Binding - drug effects</subject><subject>RNA, Small Interfering - 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is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1</title><author>Yamada, Masami ; Toba, Shiori ; Takitoh, Takako ; Yoshida, Yuko ; Mori, Daisuke ; Nakamura, Takeshi ; Iwane, Atsuko H ; Yanagida, Toshio ; Imai, Hiroshi ; Yu-Lee, Li-yuan ; Schroer, Trina ; Wynshaw-Boris, Anthony ; Hirotsune, Shinji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5768-9ec692c3d325d0b932677b4802b9d1f02648492d75a1ef467d4fa1f4307280fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>adaptor</topic><topic>Animals</topic><topic>Biological Transport - drug effects</topic><topic>Biological Transport - physiology</topic><topic>Cell Cycle Proteins - antagonists & inhibitors</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Cycle Proteins - physiology</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cells, Cultured</topic><topic>Cytoplasm - metabolism</topic><topic>Cytoplasmic Dyneins - metabolism</topic><topic>Dynactin Complex</topic><topic>dynein</topic><topic>EMBO20</topic><topic>Ganglia, Spinal - metabolism</topic><topic>Kinesin - metabolism</topic><topic>Kinesin - physiology</topic><topic>kinesin-1</topic><topic>Lis1</topic><topic>Mammals</topic><topic>Mice</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>mNUDC</topic><topic>Models, Biological</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Nuclear Proteins - antagonists & inhibitors</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nuclear Proteins - physiology</topic><topic>Protein Binding - drug effects</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Masami</creatorcontrib><creatorcontrib>Toba, 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Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Yamada, Masami</au><au>Toba, Shiori</au><au>Takitoh, Takako</au><au>Yoshida, Yuko</au><au>Mori, Daisuke</au><au>Nakamura, Takeshi</au><au>Iwane, Atsuko H</au><au>Yanagida, Toshio</au><au>Imai, Hiroshi</au><au>Yu-Lee, Li-yuan</au><au>Schroer, Trina</au><au>Wynshaw-Boris, Anthony</au><au>Hirotsune, Shinji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2010-02-03</date><risdate>2010</risdate><volume>29</volume><issue>3</issue><spage>517</spage><epage>531</epage><pages>517-531</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Lissencephaly is a devastating neurological disorder caused by defective neuronal migration. The
LIS1
(or
PAFAH1B1
) gene was identified as the gene mutated in lissencephaly patients, and was found to regulate cytoplasmic dynein function and localization. In particular, LIS1 is essential for anterograde transport of cytoplasmic dynein as a part of the cytoplasmic dynein–LIS1–microtubule complex in a kinesin‐1‐dependent manner. However, the underlying mechanism by which a cytoplasmic dynein–LIS1–microtubule complex binds kinesin‐1 is unknown. Here, we report that mNUDC (mammalian NUDC) interacts with kinesin‐1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin‐1. mNUDC is also required for anterograde transport of a dynactin‐containing complex. Inhibition of mNUDC severely suppressed anterograde transport of distinct cytoplasmic dynein and dynactin complexes, whereas motility of kinesin‐1 remained intact. Reconstruction experiments clearly demonstrated that mNUDC mediates the interaction of the dynein or dynactin complex with kinesin‐1 and supports their transport by kinesin‐1. Our findings have uncovered an essential role of mNUDC for anterograde transport of dynein and dynactin by kinesin‐1.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>20019668</pmid><doi>10.1038/emboj.2009.378</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature OA Free Journals |
| subjects | adaptor Animals Biological Transport - drug effects Biological Transport - physiology Cell Cycle Proteins - antagonists & inhibitors Cell Cycle Proteins - metabolism Cell Cycle Proteins - physiology Cell Membrane - drug effects Cell Membrane - metabolism Cells, Cultured Cytoplasm - metabolism Cytoplasmic Dyneins - metabolism Dynactin Complex dynein EMBO20 Ganglia, Spinal - metabolism Kinesin - metabolism Kinesin - physiology kinesin-1 Lis1 Mammals Mice Microtubule-Associated Proteins - metabolism mNUDC Models, Biological Neurons - drug effects Neurons - metabolism Nuclear Proteins - antagonists & inhibitors Nuclear Proteins - metabolism Nuclear Proteins - physiology Protein Binding - drug effects RNA, Small Interfering - pharmacology Swine |
| title | mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1 |
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