Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility.
We have previously identified the scaffold protein liprin-α1 as an important regulator of integrin-mediated cell motility and tumor cell invasion. Liprin-α1 may interact with different proteins, and the functional significance of these interactions in the regulation of cell motility is poorly known....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3113849?pdf=render |
| _version_ | 1818133799483998208 |
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| author | Claudia Asperti Veronica Astro Emanuela Pettinato Simona Paris Angela Bachi Ivan de Curtis |
| author_facet | Claudia Asperti Veronica Astro Emanuela Pettinato Simona Paris Angela Bachi Ivan de Curtis |
| author_sort | Claudia Asperti |
| collection | DOAJ |
| description | We have previously identified the scaffold protein liprin-α1 as an important regulator of integrin-mediated cell motility and tumor cell invasion. Liprin-α1 may interact with different proteins, and the functional significance of these interactions in the regulation of cell motility is poorly known. Here we have addressed the involvement of the liprin-α1 partner GIT1 in liprin-α1-mediated effects on cell spreading and migration. GIT1 depletion inhibited spreading by affecting the lamellipodia, and prevented liprin-α1-enhanced spreading. Conversely inhibition of the formation of the liprin-α1-GIT complex by expression of liprin-ΔCC3 could still enhance spreading, although to a lesser extent compared to full length liprin-α1. No cumulative effects were observed after depletion of both liprin-α1 and GIT1, suggesting that the two proteins belong to the same signaling network in the regulation of cell spreading. Our data suggest that liprin-α1 may compete with paxillin for binding to GIT1, while binding of βPIX to GIT1 was unaffected by the presence of liprin-α1. Interestingly, GIT and liprin-α1 reciprocally regulated their subcellular localization, since liprin-α1 overexpression, but not the GIT binding-defective liprin-ΔCC3 mutant, affected the localization of endogenous GIT at peripheral and mature central focal adhesions, while the expression of a truncated, active form of GIT1 enhanced the localization of endogenous liprin-α1 at the edge of spreading cells. Moreover, GIT1 was required for liprin-α1-enhanced haptotatic migration, although the direct interaction between liprin-α1 and GIT1 was not needed. Our findings show that the functional interaction between liprin-α1 and GIT1 cooperate in the regulation of integrin-dependent cell spreading and motility on extracellular matrix. These findings and the possible competition of liprin-α1 with paxillin for binding to GIT1 suggest that alternative binding of GIT1 to either liprin-α1 or paxillin plays distinct roles in different phases of the protrusive activity in the cell. |
| first_indexed | 2024-12-11T08:58:28Z |
| format | Article |
| id | doaj.art-44f66f669c674c69bab1211f629900e8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T08:58:28Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-44f66f669c674c69bab1211f629900e82022-12-22T01:13:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2075710.1371/journal.pone.0020757Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility.Claudia AspertiVeronica AstroEmanuela PettinatoSimona ParisAngela BachiIvan de CurtisWe have previously identified the scaffold protein liprin-α1 as an important regulator of integrin-mediated cell motility and tumor cell invasion. Liprin-α1 may interact with different proteins, and the functional significance of these interactions in the regulation of cell motility is poorly known. Here we have addressed the involvement of the liprin-α1 partner GIT1 in liprin-α1-mediated effects on cell spreading and migration. GIT1 depletion inhibited spreading by affecting the lamellipodia, and prevented liprin-α1-enhanced spreading. Conversely inhibition of the formation of the liprin-α1-GIT complex by expression of liprin-ΔCC3 could still enhance spreading, although to a lesser extent compared to full length liprin-α1. No cumulative effects were observed after depletion of both liprin-α1 and GIT1, suggesting that the two proteins belong to the same signaling network in the regulation of cell spreading. Our data suggest that liprin-α1 may compete with paxillin for binding to GIT1, while binding of βPIX to GIT1 was unaffected by the presence of liprin-α1. Interestingly, GIT and liprin-α1 reciprocally regulated their subcellular localization, since liprin-α1 overexpression, but not the GIT binding-defective liprin-ΔCC3 mutant, affected the localization of endogenous GIT at peripheral and mature central focal adhesions, while the expression of a truncated, active form of GIT1 enhanced the localization of endogenous liprin-α1 at the edge of spreading cells. Moreover, GIT1 was required for liprin-α1-enhanced haptotatic migration, although the direct interaction between liprin-α1 and GIT1 was not needed. Our findings show that the functional interaction between liprin-α1 and GIT1 cooperate in the regulation of integrin-dependent cell spreading and motility on extracellular matrix. These findings and the possible competition of liprin-α1 with paxillin for binding to GIT1 suggest that alternative binding of GIT1 to either liprin-α1 or paxillin plays distinct roles in different phases of the protrusive activity in the cell.http://europepmc.org/articles/PMC3113849?pdf=render |
| spellingShingle | Claudia Asperti Veronica Astro Emanuela Pettinato Simona Paris Angela Bachi Ivan de Curtis Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility. PLoS ONE |
| title | Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility. |
| title_full | Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility. |
| title_fullStr | Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility. |
| title_full_unstemmed | Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility. |
| title_short | Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility. |
| title_sort | biochemical and functional characterization of the interaction between liprin α1 and git1 implications for the regulation of cell motility |
| url | http://europepmc.org/articles/PMC3113849?pdf=render |
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