Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules
Summary The generation of cellular microtubules is initiated at specific sites such as the centrosome and the Golgi apparatus that contain nucleation complexes rich in γ-tubulin. The microtubule growing plus-ends are stabilized by plus-end tracking proteins (+TIPs), mainly EB1 and associated protein...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2012-12-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/2/2/238 |
| _version_ | 1818859380373716992 |
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| author | Régine Roubin Claire Acquaviva Véronique Chevrier Fatima Sedjaï Déborah Zyss Daniel Birnbaum Olivier Rosnet |
| author_facet | Régine Roubin Claire Acquaviva Véronique Chevrier Fatima Sedjaï Déborah Zyss Daniel Birnbaum Olivier Rosnet |
| author_sort | Régine Roubin |
| collection | DOAJ |
| description | Summary
The generation of cellular microtubules is initiated at specific sites such as the centrosome and the Golgi apparatus that contain nucleation complexes rich in γ-tubulin. The microtubule growing plus-ends are stabilized by plus-end tracking proteins (+TIPs), mainly EB1 and associated proteins. Myomegalin was identified as a centrosome/Golgi protein associated with cyclic nucleotide phosphodiesterase. We show here that Myomegalin exists as several isoforms. We characterize two of them. One isoform, CM-MMG, harbors a conserved domain (CM1), recently described as a nucleation activator, and is related to a family of γ-tubulin binding proteins, which includes Drosophila centrosomin. It localizes at the centrosome and at the cis-Golgi in an AKAP450-dependent manner. It recruits γ-tubulin nucleating complexes and promotes microtubule nucleation. The second isoform, EB-MMG, is devoid of CM1 domain and has a unique N-terminus with potential EB1-binding sites. It localizes at the cis-Golgi and can localize to microtubule plus-ends. EB-MMG binds EB1 and affects its loading on microtubules and microtubule growth. Depletion of Myomegalin by small interfering RNA delays microtubule growth from the centrosome and Golgi apparatus, and decreases directional migration of RPE1 cells. In conclusion, the Myomegalin gene encodes different isoforms that regulate microtubules. At least two of these have different roles, demonstrating a previously unknown mechanism to control microtubules in vertebrate cells. |
| first_indexed | 2024-12-19T09:11:16Z |
| format | Article |
| id | doaj.art-2bcef251df934afa8ef0e5c8625f1316 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T09:11:16Z |
| publishDate | 2012-12-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-2bcef251df934afa8ef0e5c8625f13162022-12-21T20:28:11ZengThe Company of BiologistsBiology Open2046-63902012-12-012223825010.1242/bio.2012339220123392Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubulesRégine Roubin0Claire Acquaviva1Véronique Chevrier2Fatima Sedjaï3Déborah Zyss4Daniel Birnbaum5Olivier Rosnet6 Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, F-13009 Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, F-13009 Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, F-13009 Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, F-13009 Marseille, France Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, F-13009 Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, F-13009 Marseille, France Summary The generation of cellular microtubules is initiated at specific sites such as the centrosome and the Golgi apparatus that contain nucleation complexes rich in γ-tubulin. The microtubule growing plus-ends are stabilized by plus-end tracking proteins (+TIPs), mainly EB1 and associated proteins. Myomegalin was identified as a centrosome/Golgi protein associated with cyclic nucleotide phosphodiesterase. We show here that Myomegalin exists as several isoforms. We characterize two of them. One isoform, CM-MMG, harbors a conserved domain (CM1), recently described as a nucleation activator, and is related to a family of γ-tubulin binding proteins, which includes Drosophila centrosomin. It localizes at the centrosome and at the cis-Golgi in an AKAP450-dependent manner. It recruits γ-tubulin nucleating complexes and promotes microtubule nucleation. The second isoform, EB-MMG, is devoid of CM1 domain and has a unique N-terminus with potential EB1-binding sites. It localizes at the cis-Golgi and can localize to microtubule plus-ends. EB-MMG binds EB1 and affects its loading on microtubules and microtubule growth. Depletion of Myomegalin by small interfering RNA delays microtubule growth from the centrosome and Golgi apparatus, and decreases directional migration of RPE1 cells. In conclusion, the Myomegalin gene encodes different isoforms that regulate microtubules. At least two of these have different roles, demonstrating a previously unknown mechanism to control microtubules in vertebrate cells.http://bio.biologists.org/content/2/2/238CentrosomeEB1GolgiMicrotubuleγ-Tubulin |
| spellingShingle | Régine Roubin Claire Acquaviva Véronique Chevrier Fatima Sedjaï Déborah Zyss Daniel Birnbaum Olivier Rosnet Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules Biology Open Centrosome EB1 Golgi Microtubule γ-Tubulin |
| title | Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules |
| title_full | Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules |
| title_fullStr | Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules |
| title_full_unstemmed | Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules |
| title_short | Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules |
| title_sort | myomegalin is necessary for the formation of centrosomal and golgi derived microtubules |
| topic | Centrosome EB1 Golgi Microtubule γ-Tubulin |
| url | http://bio.biologists.org/content/2/2/238 |
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