Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells.
<h4>Background</h4>Migrating leukocytes normally have a polarized morphology with an actin-rich lamellipodium at the front and a uropod at the rear. Microtubules (MTs) are required for persistent migration and chemotaxis, but how they affect cell polarity is not known.<h4>Methodolo...
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008774&type=printable |
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| author | Aya Takesono Sarah J Heasman Beata Wojciak-Stothard Ritu Garg Anne J Ridley |
| author_facet | Aya Takesono Sarah J Heasman Beata Wojciak-Stothard Ritu Garg Anne J Ridley |
| author_sort | Aya Takesono |
| collection | DOAJ |
| description | <h4>Background</h4>Migrating leukocytes normally have a polarized morphology with an actin-rich lamellipodium at the front and a uropod at the rear. Microtubules (MTs) are required for persistent migration and chemotaxis, but how they affect cell polarity is not known.<h4>Methodology/principal findings</h4>Here we report that T cells treated with nocodazole to disrupt MTs are unable to form a stable uropod or lamellipodium, and instead often move by membrane blebbing with reduced migratory persistence. However, uropod-localized receptors and ezrin/radixin/moesin proteins still cluster in nocodazole-treated cells, indicating that MTs are required specifically for uropod stability. Nocodazole stimulates RhoA activity, and inhibition of the RhoA target ROCK allows nocodazole-treated cells to re-establish lamellipodia and uropods and persistent migratory polarity. ROCK inhibition decreases nocodazole-induced membrane blebbing and stabilizes MTs. The myosin inhibitor blebbistatin also stabilizes MTs, indicating that RhoA/ROCK act through myosin II to destabilize MTs.<h4>Conclusions/significance</h4>Our results indicate that RhoA/ROCK signaling normally contributes to migration by affecting both actomyosin contractility and MT stability. We propose that regulation of MT stability and RhoA/ROCK activity is a mechanism to alter T-cell migratory behavior from lamellipodium-based persistent migration to bleb-based migration with frequent turning. |
| format | Article |
| id | doaj-art-c6bea63751a044e9aa9b0da3bef0d2b0 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c6bea63751a044e9aa9b0da3bef0d2b02025-08-20T02:31:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e877410.1371/journal.pone.0008774Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells.Aya TakesonoSarah J HeasmanBeata Wojciak-StothardRitu GargAnne J Ridley<h4>Background</h4>Migrating leukocytes normally have a polarized morphology with an actin-rich lamellipodium at the front and a uropod at the rear. Microtubules (MTs) are required for persistent migration and chemotaxis, but how they affect cell polarity is not known.<h4>Methodology/principal findings</h4>Here we report that T cells treated with nocodazole to disrupt MTs are unable to form a stable uropod or lamellipodium, and instead often move by membrane blebbing with reduced migratory persistence. However, uropod-localized receptors and ezrin/radixin/moesin proteins still cluster in nocodazole-treated cells, indicating that MTs are required specifically for uropod stability. Nocodazole stimulates RhoA activity, and inhibition of the RhoA target ROCK allows nocodazole-treated cells to re-establish lamellipodia and uropods and persistent migratory polarity. ROCK inhibition decreases nocodazole-induced membrane blebbing and stabilizes MTs. The myosin inhibitor blebbistatin also stabilizes MTs, indicating that RhoA/ROCK act through myosin II to destabilize MTs.<h4>Conclusions/significance</h4>Our results indicate that RhoA/ROCK signaling normally contributes to migration by affecting both actomyosin contractility and MT stability. We propose that regulation of MT stability and RhoA/ROCK activity is a mechanism to alter T-cell migratory behavior from lamellipodium-based persistent migration to bleb-based migration with frequent turning.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008774&type=printable |
| spellingShingle | Aya Takesono Sarah J Heasman Beata Wojciak-Stothard Ritu Garg Anne J Ridley Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. PLoS ONE |
| title | Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. |
| title_full | Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. |
| title_fullStr | Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. |
| title_full_unstemmed | Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. |
| title_short | Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. |
| title_sort | microtubules regulate migratory polarity through rho rock signaling in t cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008774&type=printable |
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