Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells.
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.Here we report that T cells treated with nocodazol...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2808253?pdf=render |
| _version_ | 1818925268013678592 |
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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 | 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.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.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. |
| first_indexed | 2024-12-20T02:38:31Z |
| format | Article |
| id | doaj.art-c6bea63751a044e9aa9b0da3bef0d2b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:38:31Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c6bea63751a044e9aa9b0da3bef0d2b02022-12-21T19:56:23ZengPublic 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 RidleyMigrating 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.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.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.http://europepmc.org/articles/PMC2808253?pdf=render |
| 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 | http://europepmc.org/articles/PMC2808253?pdf=render |
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