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Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays

XMAP215/Stu2/Alp14 accelerates tubulin polymerization while processively tracking microtubule (MT) plus ends via tumor overexpressed gene (TOG) domain arrays. It remains poorly understood how these functions arise from tubulin recruitment, mediated by the distinct TOG1 and TOG2 domains, or the assem...

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Autores principales: Cook, Brian D., Chang, Fred, Flor-Parra, Ignacio, Al-Bassam, Jawdat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724690/
https://www.ncbi.nlm.nih.gov/pubmed/30969896
http://dx.doi.org/10.1091/mbc.E19-02-0093
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author Cook, Brian D.
Chang, Fred
Flor-Parra, Ignacio
Al-Bassam, Jawdat
author_facet Cook, Brian D.
Chang, Fred
Flor-Parra, Ignacio
Al-Bassam, Jawdat
author_sort Cook, Brian D.
collection PubMed
description XMAP215/Stu2/Alp14 accelerates tubulin polymerization while processively tracking microtubule (MT) plus ends via tumor overexpressed gene (TOG) domain arrays. It remains poorly understood how these functions arise from tubulin recruitment, mediated by the distinct TOG1 and TOG2 domains, or the assembly of these arrays into large square complexes. Here, we describe a relationship between MT plus-end tracking and polymerase functions revealing their distinct origin within TOG arrays. We study Alp14 mutants designed based on structural models, with defects in either tubulin recruitment or self-organization. Using in vivo live imaging in fission yeast and in vitro MT dynamics assays, we show that tubulins recruited by TOG1 and TOG2 serve concerted, yet distinct, roles in MT plus-end tracking and polymerase functions. TOG1 is critical for processive plus-end tracking, whereas TOG2 is critical for accelerating tubulin polymerization. Inactivating interfaces that stabilize square complexes lead to defects in both processive MT plus-end tracking and polymerase. Our studies suggest that a dynamic cycle between square and unfurled TOG array states gives rise to processive polymerase activity at MT plus ends.
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spelling pubmed-67246902019-09-06 Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays Cook, Brian D. Chang, Fred Flor-Parra, Ignacio Al-Bassam, Jawdat Mol Biol Cell Articles XMAP215/Stu2/Alp14 accelerates tubulin polymerization while processively tracking microtubule (MT) plus ends via tumor overexpressed gene (TOG) domain arrays. It remains poorly understood how these functions arise from tubulin recruitment, mediated by the distinct TOG1 and TOG2 domains, or the assembly of these arrays into large square complexes. Here, we describe a relationship between MT plus-end tracking and polymerase functions revealing their distinct origin within TOG arrays. We study Alp14 mutants designed based on structural models, with defects in either tubulin recruitment or self-organization. Using in vivo live imaging in fission yeast and in vitro MT dynamics assays, we show that tubulins recruited by TOG1 and TOG2 serve concerted, yet distinct, roles in MT plus-end tracking and polymerase functions. TOG1 is critical for processive plus-end tracking, whereas TOG2 is critical for accelerating tubulin polymerization. Inactivating interfaces that stabilize square complexes lead to defects in both processive MT plus-end tracking and polymerase. Our studies suggest that a dynamic cycle between square and unfurled TOG array states gives rise to processive polymerase activity at MT plus ends. The American Society for Cell Biology 2019-06-01 /pmc/articles/PMC6724690/ /pubmed/30969896 http://dx.doi.org/10.1091/mbc.E19-02-0093 Text en © 2019 Cook et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Cook, Brian D.
Chang, Fred
Flor-Parra, Ignacio
Al-Bassam, Jawdat
Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
title Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
title_full Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
title_fullStr Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
title_full_unstemmed Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
title_short Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
title_sort microtubule polymerase and processive plus-end tracking functions originate from distinct features within tog domain arrays
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724690/
https://www.ncbi.nlm.nih.gov/pubmed/30969896
http://dx.doi.org/10.1091/mbc.E19-02-0093
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