Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth
Capping protein (CP) is a heterodimer that regulates actin assembly by binding to the barbed end of F-actin. In cultured nonneuronal cells, each CP subunit plays a critical role in the organization and dynamics of lamellipodia and filopodia. Mutations in either α or β CP subunit result in retinal de...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2010
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| Online Access: | http://hdl.handle.net/1721.1/52611 https://orcid.org/0000-0003-1262-0592 |
| _version_ | 1826212881165713408 |
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| author | Davis, David A. Wilson, Meredith H. Giraud, Jodel Xe, Zhigang Tseng, Huang-Chun England, Cheryl Herscovitz, Haya Tseng, Huang-Chun Delalle, Ivana |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Davis, David A. Wilson, Meredith H. Giraud, Jodel Xe, Zhigang Tseng, Huang-Chun England, Cheryl Herscovitz, Haya Tseng, Huang-Chun Delalle, Ivana |
| author_sort | Davis, David A. |
| collection | MIT |
| description | Capping protein (CP) is a heterodimer that regulates actin assembly by binding to the barbed end of F-actin. In cultured nonneuronal cells, each CP subunit plays a critical role in the organization and dynamics of lamellipodia and filopodia. Mutations in either α or β CP subunit result in retinal degeneration in Drosophila. However, the function of CP subunits in mammalian neurons remains unclear. Here, we investigate the role of the β CP subunit expressed in the brain, Capzb2, in growth cone morphology and neurite outgrowth. We found that silencing Capzb2 in hippocampal neurons resulted in short neurites and misshapen growth cones in which microtubules overgrew into the periphery and completely overlapped with F-actin. In searching for the mechanisms underlying these cytoskeletal abnormalities, we identified β-tubulin as a novel binding partner of Capzb2 and demonstrated that Capzb2 decreases the rate and the extent of tubulin polymerization in vitro. We mapped the region of Capzb2 that was required for the subunit to interact with β-tubulin and inhibit microtubule polymerization. A mutant Capzb2 lacking this region was able to bind F-actin and form a CP heterodimer with α2-subunit. However, this mutant was unable to rescue the growth cone and neurite outgrowth phenotypes caused by Capzb2 knockdown. Together, these data suggest that Capzb2 plays an important role in growth cone formation and neurite outgrowth and that the underlying mechanism may involve direct interaction between Capzb2 and microtubules. |
| first_indexed | 2024-09-23T15:39:55Z |
| format | Article |
| id | mit-1721.1/52611 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:39:55Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/526112022-09-29T15:18:57Z Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth Davis, David A. Wilson, Meredith H. Giraud, Jodel Xe, Zhigang Tseng, Huang-Chun England, Cheryl Herscovitz, Haya Tseng, Huang-Chun Delalle, Ivana Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Tsai, Li-Huei Giraud, Jodel Tseng, Huang-Chun Tsai, Li-Huei Capping protein (CP) is a heterodimer that regulates actin assembly by binding to the barbed end of F-actin. In cultured nonneuronal cells, each CP subunit plays a critical role in the organization and dynamics of lamellipodia and filopodia. Mutations in either α or β CP subunit result in retinal degeneration in Drosophila. However, the function of CP subunits in mammalian neurons remains unclear. Here, we investigate the role of the β CP subunit expressed in the brain, Capzb2, in growth cone morphology and neurite outgrowth. We found that silencing Capzb2 in hippocampal neurons resulted in short neurites and misshapen growth cones in which microtubules overgrew into the periphery and completely overlapped with F-actin. In searching for the mechanisms underlying these cytoskeletal abnormalities, we identified β-tubulin as a novel binding partner of Capzb2 and demonstrated that Capzb2 decreases the rate and the extent of tubulin polymerization in vitro. We mapped the region of Capzb2 that was required for the subunit to interact with β-tubulin and inhibit microtubule polymerization. A mutant Capzb2 lacking this region was able to bind F-actin and form a CP heterodimer with α2-subunit. However, this mutant was unable to rescue the growth cone and neurite outgrowth phenotypes caused by Capzb2 knockdown. Together, these data suggest that Capzb2 plays an important role in growth cone formation and neurite outgrowth and that the underlying mechanism may involve direct interaction between Capzb2 and microtubules. 2010-03-16T14:50:53Z 2010-03-16T14:50:53Z 2009-10 2009-04 Article http://purl.org/eprint/type/JournalArticle http://hdl.handle.net/1721.1/52611 Davis, David A. et al. “Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth.” Ed. Manfred Schliwa. PLoS Biology 7.10 (2009): e1000208. 19806181 https://orcid.org/0000-0003-1262-0592 en_US http://dx.doi.org/10.1371/journal.pbio.1000208 PLoS Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Davis, David A. Wilson, Meredith H. Giraud, Jodel Xe, Zhigang Tseng, Huang-Chun England, Cheryl Herscovitz, Haya Tseng, Huang-Chun Delalle, Ivana Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth |
| title | Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth |
| title_full | Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth |
| title_fullStr | Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth |
| title_full_unstemmed | Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth |
| title_short | Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth |
| title_sort | capzb2 interacts with β tubulin to regulate growth cone morphology and neurite outgrowth |
| url | http://hdl.handle.net/1721.1/52611 https://orcid.org/0000-0003-1262-0592 |
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