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dc.contributor.authorKawaguchi, Nobuko
dc.contributor.authorSundberg, Christina
dc.contributor.authorKveiborg, Marie
dc.contributor.authorMoghadaszadeh, Behzad
dc.contributor.authorAsmar, Meena
dc.contributor.authorDietrich, Nikolaj
dc.contributor.authorThodeti, Charles Kumar
dc.contributor.authorNielsen, Finn C.
dc.contributor.authorMoller, Peter
dc.contributor.authorMercurio, Arthur M.
dc.contributor.authorAlbrechtsen, Reidar
dc.contributor.authorWewer, Ulla M.
dc.date2022-08-11T08:08:02.000
dc.date.accessioned2022-08-23T15:39:47Z
dc.date.available2022-08-23T15:39:47Z
dc.date.issued2003-08-14
dc.date.submitted2010-11-07
dc.identifier.citationJ Cell Sci. 2003 Oct 1;116(Pt 19):3893-904. Epub 2003 Aug 12. <a href="http://dx.doi.org/10.1242/jcs.00699">Link to article on publisher's site</a>
dc.identifier.issn0021-9533 (Linking)
dc.identifier.doi10.1242/jcs.00699
dc.identifier.pmid12915587
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26253
dc.description.abstractChanges in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=12915587&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectADAM Proteins
dc.subjectActins
dc.subjectAdipocytes
dc.subjectAnimals
dc.subjectAntigens, CD29
dc.subjectCell Adhesion
dc.subjectCell Differentiation
dc.subjectCell Size
dc.subjectCells, Cultured
dc.subjectCloning, Molecular
dc.subjectCricetinae
dc.subjectCricetulus
dc.subjectCytoskeleton
dc.subjectExtracellular Matrix
dc.subjectFibronectins
dc.subjectFlow Cytometry
dc.subjectHumans
dc.subjectMembrane Proteins
dc.subjectMetalloendopeptidases
dc.subjectMice
dc.subjectOctoxynol
dc.subjectProtein Binding
dc.subjectRNA, Small Interfering
dc.subjectRetroviridae
dc.subjectStress Fibers
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function
dc.typeArticle
dc.source.journaltitleJournal of cell science
dc.source.volume116
dc.source.issuePt 19
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1167&amp;context=cancerbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/167
dc.identifier.contextkey1633392
refterms.dateFOA2022-08-23T15:39:47Z
html.description.abstract<p>Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation.</p>
dc.identifier.submissionpathcancerbiology_pp/167
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages3893-904


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