Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing
The formin protein formin-like 1 (FMNL1) is highly restrictedly expressed in hematopoietic lineage-derived cells and has been previously identified as a tumor-associated antigen. However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1γ) contai...
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| Veröffentlicht in: | The Journal of biological chemistry 2009-11, Vol.284 (48), p.33409-33417 |
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| container_title | The Journal of biological chemistry |
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| creator | Han, Yanyan Eppinger, Elfriede Schuster, Ingrid G. Weigand, Luise U. Liang, Xiaoling Kremmer, Elisabeth Peschel, Christian Krackhardt, Angela M. |
| description | The formin protein formin-like 1 (FMNL1) is highly restrictedly expressed in hematopoietic lineage-derived cells and has been previously identified as a tumor-associated antigen. However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1γ) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1γ is specifically located at the cell membrane and cortex in diverse cell lines. Similar localization of FMNL1 was observed for a mutant lacking the DAD domain (FMNL1ΔDAD), indicating that deregulation of autoinhibition is effective in FMNL1γ. Expression of both FMNL1γ and FMNL1ΔDAD induces polarized nonapoptotic blebbing that is dependent on N-terminal myristoylation of FMNL1 but independent of Src and ROCK activity. Thus, our results describe N-myristoylation as a regulative mechanism of FMNL1 responsible for membrane trafficking potentially involved in a diversity of polarized processes of hematopoietic lineage-derived cells. |
| doi_str_mv | 10.1074/jbc.M109.060699 |
| format | Article |
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However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1γ) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1γ is specifically located at the cell membrane and cortex in diverse cell lines. Similar localization of FMNL1 was observed for a mutant lacking the DAD domain (FMNL1ΔDAD), indicating that deregulation of autoinhibition is effective in FMNL1γ. Expression of both FMNL1γ and FMNL1ΔDAD induces polarized nonapoptotic blebbing that is dependent on N-terminal myristoylation of FMNL1 but independent of Src and ROCK activity. Thus, our results describe N-myristoylation as a regulative mechanism of FMNL1 responsible for membrane trafficking potentially involved in a diversity of polarized processes of hematopoietic lineage-derived cells.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M109.060699</identifier><identifier>PMID: 19815554</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alternative Splicing ; Binding Sites ; Cell Line ; Cell Line, Tumor ; Cell Membrane - metabolism ; Cells, Cultured ; Cloning, Molecular ; Cytoskeletal Proteins - chemistry ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; DNA, Complementary - chemistry ; DNA, Complementary - genetics ; Formins ; Humans ; Immunoblotting ; K562 Cells ; Membrane Transport, Structure, Function, and Biogenesis ; Microscopy, Confocal ; Molecular Sequence Data ; Mutation ; Myristic Acid - metabolism ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Transport ; Reverse Transcriptase Polymerase Chain Reaction ; rho-Associated Kinases - metabolism ; Sequence Analysis, DNA ; src-Family Kinases - metabolism</subject><ispartof>The Journal of biological chemistry, 2009-11, Vol.284 (48), p.33409-33417</ispartof><rights>2009 © 2009 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2009 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-aa2c361dce6c9ab1b9262ea053286949e3128d0d7b4fe79978ed2f53bec615e33</citedby><cites>FETCH-LOGICAL-c495t-aa2c361dce6c9ab1b9262ea053286949e3128d0d7b4fe79978ed2f53bec615e33</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/PMC2785185/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785185/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,729,782,786,887,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19815554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Yanyan</creatorcontrib><creatorcontrib>Eppinger, Elfriede</creatorcontrib><creatorcontrib>Schuster, Ingrid G.</creatorcontrib><creatorcontrib>Weigand, Luise U.</creatorcontrib><creatorcontrib>Liang, Xiaoling</creatorcontrib><creatorcontrib>Kremmer, Elisabeth</creatorcontrib><creatorcontrib>Peschel, Christian</creatorcontrib><creatorcontrib>Krackhardt, Angela M.</creatorcontrib><title>Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The formin protein formin-like 1 (FMNL1) is highly restrictedly expressed in hematopoietic lineage-derived cells and has been previously identified as a tumor-associated antigen. However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1γ) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1γ is specifically located at the cell membrane and cortex in diverse cell lines. Similar localization of FMNL1 was observed for a mutant lacking the DAD domain (FMNL1ΔDAD), indicating that deregulation of autoinhibition is effective in FMNL1γ. Expression of both FMNL1γ and FMNL1ΔDAD induces polarized nonapoptotic blebbing that is dependent on N-terminal myristoylation of FMNL1 but independent of Src and ROCK activity. Thus, our results describe N-myristoylation as a regulative mechanism of FMNL1 responsible for membrane trafficking potentially involved in a diversity of polarized processes of hematopoietic lineage-derived cells.</description><subject>Alternative Splicing</subject><subject>Binding Sites</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Cloning, Molecular</subject><subject>Cytoskeletal Proteins - chemistry</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>DNA, Complementary - chemistry</subject><subject>DNA, Complementary - genetics</subject><subject>Formins</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>K562 Cells</subject><subject>Membrane Transport, Structure, Function, and Biogenesis</subject><subject>Microscopy, Confocal</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Myristic Acid - metabolism</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Transport</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>rho-Associated Kinases - metabolism</subject><subject>Sequence Analysis, DNA</subject><subject>src-Family Kinases - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1vEzEQhlcIREPhzA18QCocNvXnrn1BohWBSElBQCVulu2dbFx218XeFIVfj6ON-Djgiw_zzOvxPEXxlOA5wTU_v7FuviZYzXGFK6XuFTOCJSuZIF_vFzOMKSkVFfKkeJTSDc6HK_KwOCFKEiEEnxXtIsTeD2XnvwEi6OVifbUir9AyoU_Q7jozQoPsHl2VIxw406H1Pvo0hn2u-TAgMzRoOTQ7Bwl9DJ2J_mduWUNvoxkAXXRgrR_ax8WDjekSPDnep8X14u2Xy_fl6sO75eWbVem4EmNpDHWsIo2DyiljiVW0omCwYFRWiitghMoGN7XlG6iVqiU0dCOYBVcRAYydFq-n3Nud7SHnDGM0nb6Nvjdxr4Px-t_K4Le6DXea1lIQKXLA2TEghu87SKPufXLQdfk3YZd0zTgRVGCeyfOJdDGkFGHz-xWC9cGOznb0wY6e7OSOZ38P94c_6sjAiwnY-nb7w0fQ1ge3hV5TyTWXmjGODznPJ2xjgjZt9qGvP1NMGCZ1XhWXmVATAXnXdx6iTs7D4KDJoW7UTfD_nfIXneu0Gg</recordid><startdate>20091127</startdate><enddate>20091127</enddate><creator>Han, Yanyan</creator><creator>Eppinger, Elfriede</creator><creator>Schuster, Ingrid G.</creator><creator>Weigand, Luise U.</creator><creator>Liang, Xiaoling</creator><creator>Kremmer, Elisabeth</creator><creator>Peschel, Christian</creator><creator>Krackhardt, Angela M.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091127</creationdate><title>Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing</title><author>Han, Yanyan ; Eppinger, Elfriede ; Schuster, Ingrid G. ; Weigand, Luise U. ; Liang, Xiaoling ; Kremmer, Elisabeth ; Peschel, Christian ; Krackhardt, Angela M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-aa2c361dce6c9ab1b9262ea053286949e3128d0d7b4fe79978ed2f53bec615e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alternative Splicing</topic><topic>Binding Sites</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Cells, Cultured</topic><topic>Cloning, Molecular</topic><topic>Cytoskeletal Proteins - chemistry</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>DNA, Complementary - chemistry</topic><topic>DNA, Complementary - genetics</topic><topic>Formins</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>K562 Cells</topic><topic>Membrane Transport, Structure, Function, and Biogenesis</topic><topic>Microscopy, Confocal</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Myristic Acid - metabolism</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Transport</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>rho-Associated Kinases - metabolism</topic><topic>Sequence Analysis, DNA</topic><topic>src-Family Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Yanyan</creatorcontrib><creatorcontrib>Eppinger, Elfriede</creatorcontrib><creatorcontrib>Schuster, Ingrid G.</creatorcontrib><creatorcontrib>Weigand, Luise U.</creatorcontrib><creatorcontrib>Liang, Xiaoling</creatorcontrib><creatorcontrib>Kremmer, Elisabeth</creatorcontrib><creatorcontrib>Peschel, Christian</creatorcontrib><creatorcontrib>Krackhardt, Angela M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Yanyan</au><au>Eppinger, Elfriede</au><au>Schuster, Ingrid G.</au><au>Weigand, Luise U.</au><au>Liang, Xiaoling</au><au>Kremmer, Elisabeth</au><au>Peschel, Christian</au><au>Krackhardt, Angela M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2009-11-27</date><risdate>2009</risdate><volume>284</volume><issue>48</issue><spage>33409</spage><epage>33417</epage><pages>33409-33417</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The formin protein formin-like 1 (FMNL1) is highly restrictedly expressed in hematopoietic lineage-derived cells and has been previously identified as a tumor-associated antigen. However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1γ) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1γ is specifically located at the cell membrane and cortex in diverse cell lines. Similar localization of FMNL1 was observed for a mutant lacking the DAD domain (FMNL1ΔDAD), indicating that deregulation of autoinhibition is effective in FMNL1γ. Expression of both FMNL1γ and FMNL1ΔDAD induces polarized nonapoptotic blebbing that is dependent on N-terminal myristoylation of FMNL1 but independent of Src and ROCK activity. Thus, our results describe N-myristoylation as a regulative mechanism of FMNL1 responsible for membrane trafficking potentially involved in a diversity of polarized processes of hematopoietic lineage-derived cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19815554</pmid><doi>10.1074/jbc.M109.060699</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alternative Splicing Binding Sites Cell Line Cell Line, Tumor Cell Membrane - metabolism Cells, Cultured Cloning, Molecular Cytoskeletal Proteins - chemistry Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism DNA, Complementary - chemistry DNA, Complementary - genetics Formins Humans Immunoblotting K562 Cells Membrane Transport, Structure, Function, and Biogenesis Microscopy, Confocal Molecular Sequence Data Mutation Myristic Acid - metabolism Protein Isoforms - genetics Protein Isoforms - metabolism Protein Transport Reverse Transcriptase Polymerase Chain Reaction rho-Associated Kinases - metabolism Sequence Analysis, DNA src-Family Kinases - metabolism |
| title | Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing |
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