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dc.contributor.authorBhuwania, Ridhirama
dc.contributor.authorCornfine, Susanne
dc.contributor.authorFang, Zhiyou
dc.contributor.authorKruger, Marcus
dc.contributor.authorLuna, Elizabeth J.
dc.contributor.authorLinder, Stefan
dc.date2022-08-11T08:09:18.000
dc.date.accessioned2022-08-23T16:25:51Z
dc.date.available2022-08-23T16:25:51Z
dc.date.issued2012-02-17
dc.date.submitted2012-03-28
dc.identifier.citationJ Cell Sci. 2012 Feb 17. <a href="http://dx.doi.org/10.1242/jcs.100032">Link to article on publisher's site</a>
dc.identifier.issn0021-9533 (Linking)
dc.identifier.doi10.1242/jcs.100032
dc.identifier.pmid22344260
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36435
dc.description.abstractPodosomes are actin-rich adhesion and invasion structures. Especially in macrophages, podosomes exist in two subpopulations, large precursors at the cell periphery and smaller podosomes (successors) in the cell interior. To date, the mechanisms that differentially regulate these subpopulations are largely unknown. Here, we show that the membrane-associated protein supervillin localizes preferentially to successor podosomes and becomes enriched at precursors immediately prior to their dissolution. Consistently, podosome numbers are inversely correlated with supervillin protein levels. Using deletion constructs, we find that the myosin II-regulatory N-terminus of supervillin (SV 1-174) is crucial for these effects. Phosphorylated myosin light chain (pMLC) localizes at supervillin-positive podosomes, and time-lapse analyses show that enrichment of GFP-supervillin at podosomes coincides with their coupling to contractile myosin IIA-positive cables. We also show that supervillin binds only to activated myosin IIA, and a dysregulated N-terminal construct (SV 1-830) enhances pMLC levels at podosomes. Thus, preferential recruitment of supervillin to podosome subpopulations may both require and induce actomyosin contractility. Using siRNA and pharmacological inhibition, we demonstrate that supervillin and myosin IIA cooperate to regulate podosome lifetime, podosomal matrix degradation and cell polarization. In sum, we show here that podosome subpopulations differ in their molecular composition and identify supervillin, in cooperation with myosin IIA, as a critical factor in the regulation of podosome turnover and function.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22344260&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1242/jcs.100032
dc.subjectMembrane Proteins
dc.subjectMicrofilament Proteins
dc.subjectNonmuscle Myosin Type IIA
dc.subjectCell Biology
dc.titleSupervillin couples myosin-dependent contractility to podosomes and enables their turnover
dc.typeJournal Article
dc.source.journaltitleJournal of cell science
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/luna/3
dc.identifier.contextkey2706200
html.description.abstract<p>Podosomes are actin-rich adhesion and invasion structures. Especially in macrophages, podosomes exist in two subpopulations, large precursors at the cell periphery and smaller podosomes (successors) in the cell interior. To date, the mechanisms that differentially regulate these subpopulations are largely unknown. Here, we show that the membrane-associated protein supervillin localizes preferentially to successor podosomes and becomes enriched at precursors immediately prior to their dissolution. Consistently, podosome numbers are inversely correlated with supervillin protein levels. Using deletion constructs, we find that the myosin II-regulatory N-terminus of supervillin (SV 1-174) is crucial for these effects. Phosphorylated myosin light chain (pMLC) localizes at supervillin-positive podosomes, and time-lapse analyses show that enrichment of GFP-supervillin at podosomes coincides with their coupling to contractile myosin IIA-positive cables. We also show that supervillin binds only to activated myosin IIA, and a dysregulated N-terminal construct (SV 1-830) enhances pMLC levels at podosomes. Thus, preferential recruitment of supervillin to podosome subpopulations may both require and induce actomyosin contractility. Using siRNA and pharmacological inhibition, we demonstrate that supervillin and myosin IIA cooperate to regulate podosome lifetime, podosomal matrix degradation and cell polarization. In sum, we show here that podosome subpopulations differ in their molecular composition and identify supervillin, in cooperation with myosin IIA, as a critical factor in the regulation of podosome turnover and function.</p>
dc.identifier.submissionpathluna/3
dc.contributor.departmentDepartment of Cell Biology


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