Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse.
Actin depolymerizing factor-homology (ADF-H) family proteins regulate actin filament dynamics at multiple cellular locations. Herein, we have investigated the function of the ADF-H family member coactosin-like 1 (COTL1) in the regulation of actin dynamics at the T cell immune synapse (IS). We initia...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3890291?pdf=render |
| _version_ | 1811192079433334784 |
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| author | Joanna Kim Michael J Shapiro Adebowale O Bamidele Pinar Gurel Puspa Thapa Henry N Higgs Karen E Hedin Virginia S Shapiro Daniel D Billadeau |
| author_facet | Joanna Kim Michael J Shapiro Adebowale O Bamidele Pinar Gurel Puspa Thapa Henry N Higgs Karen E Hedin Virginia S Shapiro Daniel D Billadeau |
| author_sort | Joanna Kim |
| collection | DOAJ |
| description | Actin depolymerizing factor-homology (ADF-H) family proteins regulate actin filament dynamics at multiple cellular locations. Herein, we have investigated the function of the ADF-H family member coactosin-like 1 (COTL1) in the regulation of actin dynamics at the T cell immune synapse (IS). We initially identified COTL1 in a genetic screen to identify novel regulators of T cell activation, and subsequently found that it associates with F-actin and localizes at the IS in response to TCR+CD28 stimulation. Live cell microscopy showed that depletion of COTL1 protein impaired T cell spreading in response to TCR ligation and abrogated lamellipodial protrusion at the T cell - B cell contact site, producing only a band of F-actin. Significantly, re-expression of wild type COTL1, but not a mutant deficient in F-actin binding could rescue these defects. In addition, COTL1 depletion reduced T cell migration. In vitro studies showed that COTL1 and cofilin compete with each other for binding to F-actin, and COTL1 protects F-actin from cofilin-mediated depolymerization. While depletion of cofilin enhanced F-actin assembly and lamellipodial protrusion at the IS, concurrent depletion of both COTL1 and cofilin restored lamellipodia formation. Taken together, our results suggest that COTL1 regulates lamellipodia dynamics in part by protecting F-actin from cofilin-mediated disassembly. |
| first_indexed | 2024-04-11T23:45:41Z |
| format | Article |
| id | doaj.art-aa4b7635dda546b7946f964eb2927511 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:45:41Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-aa4b7635dda546b7946f964eb29275112022-12-22T03:56:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8509010.1371/journal.pone.0085090Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse.Joanna KimMichael J ShapiroAdebowale O BamidelePinar GurelPuspa ThapaHenry N HiggsKaren E HedinVirginia S ShapiroDaniel D BilladeauActin depolymerizing factor-homology (ADF-H) family proteins regulate actin filament dynamics at multiple cellular locations. Herein, we have investigated the function of the ADF-H family member coactosin-like 1 (COTL1) in the regulation of actin dynamics at the T cell immune synapse (IS). We initially identified COTL1 in a genetic screen to identify novel regulators of T cell activation, and subsequently found that it associates with F-actin and localizes at the IS in response to TCR+CD28 stimulation. Live cell microscopy showed that depletion of COTL1 protein impaired T cell spreading in response to TCR ligation and abrogated lamellipodial protrusion at the T cell - B cell contact site, producing only a band of F-actin. Significantly, re-expression of wild type COTL1, but not a mutant deficient in F-actin binding could rescue these defects. In addition, COTL1 depletion reduced T cell migration. In vitro studies showed that COTL1 and cofilin compete with each other for binding to F-actin, and COTL1 protects F-actin from cofilin-mediated depolymerization. While depletion of cofilin enhanced F-actin assembly and lamellipodial protrusion at the IS, concurrent depletion of both COTL1 and cofilin restored lamellipodia formation. Taken together, our results suggest that COTL1 regulates lamellipodia dynamics in part by protecting F-actin from cofilin-mediated disassembly.http://europepmc.org/articles/PMC3890291?pdf=render |
| spellingShingle | Joanna Kim Michael J Shapiro Adebowale O Bamidele Pinar Gurel Puspa Thapa Henry N Higgs Karen E Hedin Virginia S Shapiro Daniel D Billadeau Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse. PLoS ONE |
| title | Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse. |
| title_full | Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse. |
| title_fullStr | Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse. |
| title_full_unstemmed | Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse. |
| title_short | Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse. |
| title_sort | coactosin like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse |
| url | http://europepmc.org/articles/PMC3890291?pdf=render |
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