Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration
Cell migration is a highly dynamic process that plays pivotal roles in both physiological and pathological processes. We have previously reported that p130Cas supports cell migration through the binding to Src as well as phosphorylation-dependent association with actin retrograde flow at focal adhes...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2016-04-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/5/4/499 |
| _version_ | 1818671630026539008 |
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| author | Zhihai Zhao Song Hui Tan Hiroaki Machiyama Keiko Kawauchi Keigo Araki Hiroaki Hirata Yasuhiro Sawada |
| author_facet | Zhihai Zhao Song Hui Tan Hiroaki Machiyama Keiko Kawauchi Keigo Araki Hiroaki Hirata Yasuhiro Sawada |
| author_sort | Zhihai Zhao |
| collection | DOAJ |
| description | Cell migration is a highly dynamic process that plays pivotal roles in both physiological and pathological processes. We have previously reported that p130Cas supports cell migration through the binding to Src as well as phosphorylation-dependent association with actin retrograde flow at focal adhesions. However, it remains elusive how phosphorylated Cas interacts with actin cytoskeletons. We observe that the actin-binding protein, tensin 1, co-localizes with Cas, but not with its phosphorylation-defective mutant, at focal adhesions in leading regions of migrating cells. While a truncation mutant of tensin 1 that lacks the phosphotyrosine-binding PTB and SH2 domains (tensin 1-SH2PTB) poorly co-localizes or co-immunoprecitates with Cas, bacterially expressed recombinant tensin 1-SH2PTB protein binds to Cas in vitro in a Cas phosphorylation-dependent manner. Furthermore, exogenous expression of tensin 1-SH2PTB, which is devoid of the actin-interacting motifs, interferes with the Cas-driven cell migration, slows down the inward flux of Cas molecules, and impedes the displacement of Cas molecules from focal adhesions. Taken together, our results show that tensin 1 links inwardly moving actin cytoskeletons to phosphorylated Cas at focal adhesions, thereby driving cell migration. |
| first_indexed | 2024-12-17T07:27:03Z |
| format | Article |
| id | doaj.art-cf2d616e55bf44d8b455e6c50d5f46b8 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T07:27:03Z |
| publishDate | 2016-04-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-cf2d616e55bf44d8b455e6c50d5f46b82022-12-21T21:58:35ZengThe Company of BiologistsBiology Open2046-63902016-04-015449950610.1242/bio.016428016428Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migrationZhihai Zhao0Song Hui Tan1Hiroaki Machiyama2Keiko Kawauchi3Keigo Araki4Hiroaki Hirata5Yasuhiro Sawada6 Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Cell migration is a highly dynamic process that plays pivotal roles in both physiological and pathological processes. We have previously reported that p130Cas supports cell migration through the binding to Src as well as phosphorylation-dependent association with actin retrograde flow at focal adhesions. However, it remains elusive how phosphorylated Cas interacts with actin cytoskeletons. We observe that the actin-binding protein, tensin 1, co-localizes with Cas, but not with its phosphorylation-defective mutant, at focal adhesions in leading regions of migrating cells. While a truncation mutant of tensin 1 that lacks the phosphotyrosine-binding PTB and SH2 domains (tensin 1-SH2PTB) poorly co-localizes or co-immunoprecitates with Cas, bacterially expressed recombinant tensin 1-SH2PTB protein binds to Cas in vitro in a Cas phosphorylation-dependent manner. Furthermore, exogenous expression of tensin 1-SH2PTB, which is devoid of the actin-interacting motifs, interferes with the Cas-driven cell migration, slows down the inward flux of Cas molecules, and impedes the displacement of Cas molecules from focal adhesions. Taken together, our results show that tensin 1 links inwardly moving actin cytoskeletons to phosphorylated Cas at focal adhesions, thereby driving cell migration.http://bio.biologists.org/content/5/4/499Tensin 1P130CasActin cytoskeletonCell migrationFocal adhesion |
| spellingShingle | Zhihai Zhao Song Hui Tan Hiroaki Machiyama Keiko Kawauchi Keigo Araki Hiroaki Hirata Yasuhiro Sawada Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration Biology Open Tensin 1 P130Cas Actin cytoskeleton Cell migration Focal adhesion |
| title | Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration |
| title_full | Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration |
| title_fullStr | Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration |
| title_full_unstemmed | Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration |
| title_short | Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration |
| title_sort | association between tensin 1 and p130cas at focal adhesions links actin inward flux to cell migration |
| topic | Tensin 1 P130Cas Actin cytoskeleton Cell migration Focal adhesion |
| url | http://bio.biologists.org/content/5/4/499 |
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