c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration
Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largel...
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description | Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion. |
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Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081757</identifier><identifier>PMID: 24260586</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult Stem Cells - cytology ; Adult Stem Cells - metabolism ; Animals ; c-Met protein ; Cell adhesion & migration ; Cell Differentiation ; Cell Fusion ; Cell migration ; Cell Movement ; Cells (biology) ; Cytoskeleton ; Cytoskeleton - chemistry ; Cytoskeleton - metabolism ; Defects ; Embryo, Mammalian ; Embryogenesis ; Embryology ; Embryonic development ; Embryonic Development - genetics ; Embryonic growth stage ; Female ; Gene Expression ; Growth factors ; Injuries ; Kinases ; Lamellipodia ; Male ; Mice ; Mice, Transgenic ; Muscle Cells - cytology ; Muscle Cells - metabolism ; Muscle, Skeletal - injuries ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Muscles ; Musculoskeletal system ; Mutation ; Myoblasts ; Myoblasts, Skeletal - cytology ; Myoblasts, Skeletal - metabolism ; Myocytes ; Nitric oxide ; Phosphorylation ; Protein-tyrosine kinase receptors ; Proteins ; Proto-Oncogene Proteins c-met - genetics ; Proto-Oncogene Proteins c-met - metabolism ; Pseudopodia ; Pseudopodia - metabolism ; Regeneration ; Regeneration - genetics ; Rodents ; Satellite cells ; Skeletal muscle ; Stem cell transplantation ; Stem cells ; Tyrosine</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e81757-e81757</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Webster, Fan. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Webster, Fan 2013 Webster, Fan</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-6515b62be12b4c52839c6c2607ee616dd31d2737d84694ee0dbf9b625b0dc61d3</citedby><cites>FETCH-LOGICAL-c758t-6515b62be12b4c52839c6c2607ee616dd31d2737d84694ee0dbf9b625b0dc61d3</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/PMC3834319/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834319/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24260586$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mouly, Vincent</contributor><creatorcontrib>Webster, Micah T</creatorcontrib><creatorcontrib>Fan, Chen-Ming</creatorcontrib><title>c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.</description><subject>Adult Stem Cells - cytology</subject><subject>Adult Stem Cells - metabolism</subject><subject>Animals</subject><subject>c-Met protein</subject><subject>Cell adhesion & migration</subject><subject>Cell Differentiation</subject><subject>Cell Fusion</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cells (biology)</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - chemistry</subject><subject>Cytoskeleton - metabolism</subject><subject>Defects</subject><subject>Embryo, Mammalian</subject><subject>Embryogenesis</subject><subject>Embryology</subject><subject>Embryonic development</subject><subject>Embryonic Development - genetics</subject><subject>Embryonic growth stage</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Growth factors</subject><subject>Injuries</subject><subject>Kinases</subject><subject>Lamellipodia</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Muscle Cells - cytology</subject><subject>Muscle Cells - metabolism</subject><subject>Muscle, Skeletal - injuries</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscles</subject><subject>Musculoskeletal system</subject><subject>Mutation</subject><subject>Myoblasts</subject><subject>Myoblasts, Skeletal - cytology</subject><subject>Myoblasts, Skeletal - metabolism</subject><subject>Myocytes</subject><subject>Nitric oxide</subject><subject>Phosphorylation</subject><subject>Protein-tyrosine kinase receptors</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-met - genetics</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Pseudopodia</subject><subject>Pseudopodia - metabolism</subject><subject>Regeneration</subject><subject>Regeneration - genetics</subject><subject>Rodents</subject><subject>Satellite cells</subject><subject>Skeletal muscle</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tyrosine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEoqXwDxBEQkJw2MXfTi5IVVVgpaJKUDhiOfYkm-LE29hB7L_HYdNqF_WAckg0ft53PJOZLHuO0RJTid9d-3HotVtufA9LhAosuXyQHeOSkoUgiD7c-z7KnoRwjRCnhRCPsyPCiEC8EMfZD7P4fH6VD9CMTkcIebf1ldMh5p2PrWvjNte9naJmGyGvx9D6Prfj0PZNru3oYh5-goOoXd6NwTiYvKCHQcdEPs0e1doFeDa_T7JvH86vzj4tLi4_rs5OLxZG8iIuBMe8EqQCTCpmOCloaYRJd5QAAgtrKbZEUmkLJkoGgGxVl0nAK2SNwJaeZC93vhvng5pbExRmvBSykCVLxGpHWK-v1WZoOz1sldet-hvwQ6P0ENtUgJJYG7DUlpYbVpmqpNwIkbIBQ1SSMnm9n7ONVQfWQB8H7Q5MD0_6dq0a_0vRgjKKJ4M3s8Hgb0YIUXVtMOCc7sGP070FLiRHjCT01T_o_dXNVKNTAW1f-5TXTKbqlMmCIMkJTtTyHio9FrrWpDmq2xQ_ELw9ECQmwu_Y6DEEtfr65f_Zy--H7Os9dg3axXXwbpxGJhyCbAeawYcwQH3XZIzUtAa33VDTGqh5DZLsxf4PuhPdzj39A0q4AtY</recordid><startdate>20131119</startdate><enddate>20131119</enddate><creator>Webster, Micah T</creator><creator>Fan, Chen-Ming</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131119</creationdate><title>c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration</title><author>Webster, Micah T ; Fan, Chen-Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-6515b62be12b4c52839c6c2607ee616dd31d2737d84694ee0dbf9b625b0dc61d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult Stem Cells - cytology</topic><topic>Adult Stem Cells - metabolism</topic><topic>Animals</topic><topic>c-Met protein</topic><topic>Cell adhesion & migration</topic><topic>Cell Differentiation</topic><topic>Cell Fusion</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cells (biology)</topic><topic>Cytoskeleton</topic><topic>Cytoskeleton - chemistry</topic><topic>Cytoskeleton - metabolism</topic><topic>Defects</topic><topic>Embryo, Mammalian</topic><topic>Embryogenesis</topic><topic>Embryology</topic><topic>Embryonic development</topic><topic>Embryonic Development - genetics</topic><topic>Embryonic growth stage</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Growth factors</topic><topic>Injuries</topic><topic>Kinases</topic><topic>Lamellipodia</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Muscle Cells - cytology</topic><topic>Muscle Cells - metabolism</topic><topic>Muscle, Skeletal - injuries</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscles</topic><topic>Musculoskeletal system</topic><topic>Mutation</topic><topic>Myoblasts</topic><topic>Myoblasts, Skeletal - cytology</topic><topic>Myoblasts, Skeletal - metabolism</topic><topic>Myocytes</topic><topic>Nitric oxide</topic><topic>Phosphorylation</topic><topic>Protein-tyrosine kinase receptors</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-met - genetics</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Pseudopodia</topic><topic>Pseudopodia - metabolism</topic><topic>Regeneration</topic><topic>Regeneration - genetics</topic><topic>Rodents</topic><topic>Satellite cells</topic><topic>Skeletal muscle</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Webster, Micah T</creatorcontrib><creatorcontrib>Fan, Chen-Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Webster, Micah T</au><au>Fan, Chen-Ming</au><au>Mouly, Vincent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-19</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e81757</spage><epage>e81757</epage><pages>e81757-e81757</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24260586</pmid><doi>10.1371/journal.pone.0081757</doi><tpages>e81757</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Stem Cells - cytology Adult Stem Cells - metabolism Animals c-Met protein Cell adhesion & migration Cell Differentiation Cell Fusion Cell migration Cell Movement Cells (biology) Cytoskeleton Cytoskeleton - chemistry Cytoskeleton - metabolism Defects Embryo, Mammalian Embryogenesis Embryology Embryonic development Embryonic Development - genetics Embryonic growth stage Female Gene Expression Growth factors Injuries Kinases Lamellipodia Male Mice Mice, Transgenic Muscle Cells - cytology Muscle Cells - metabolism Muscle, Skeletal - injuries Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscles Musculoskeletal system Mutation Myoblasts Myoblasts, Skeletal - cytology Myoblasts, Skeletal - metabolism Myocytes Nitric oxide Phosphorylation Protein-tyrosine kinase receptors Proteins Proto-Oncogene Proteins c-met - genetics Proto-Oncogene Proteins c-met - metabolism Pseudopodia Pseudopodia - metabolism Regeneration Regeneration - genetics Rodents Satellite cells Skeletal muscle Stem cell transplantation Stem cells Tyrosine |
title | c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration |
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