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Microtubule Polymerase and Processive Plus-end Tracking functions originate from distinct features within TOG domain arrays.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "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 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 microtubule 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 microtubule dynamics assays, we show that tubulins recruited by TOG1 and TOG2 serve concerted, yet distinct, roles in microtubule plus-end tracking and polymerase functions. TOG1 is critical for processive plus-end tracking while TOG2 is critical for accelerating tubulin polymerization. Inactivating interfaces that stabilize square complexes lead to defects in both processive microtubule 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 microtubule plus-ends. Movie S1 Movie S1 WT-Alp14-NG compared to TOG1M-NG and TOG2M-NG in vitro experiments Left, two representative movies of WT-Alp14-mNG tracking dynamic MTs. Middle, two representative movies of Alp14 TOG1M-NG tracking dynamic MTs. Left, two representative movies of Alp14 TOG2M-NG tracking dynamic MTs. Star marks signal at the MT plus end. Movie S2 Movie S2 Single molecule experiments revealing the residence of wt-Alp14-SNAP-Atto-488 compared to TOG1M-SNAP-Atto-488 single TOG2M-SNAP at MT plus ends. Left, Representative movies of WT Alp14-SNAP-Atto-488 tracking dynamic MTs.. Middle, representative movies of Alp14 TOG1M-SNAP-Atto-488 tracking dynamic MTs. Right, representative movies of Alp14 TOG2M-SNAP-Atto-488 tracking dynamic MTs. Star marks signal at the MT plus end. Movie S3 Movie S3 INT1-NG compared to INT2-NG and INT1+2-NG in vitro experiments Left, two representative movies of INT1-mNG tracking dynamic MTs. Star marks signal at the MT plus end. Middle, two representative movies of INT2-mNG tracking dynamic MTs. Star marks signal at the MT plus end. Left, two representative movies of INT1+2-mNG tracking dynamic MTs. Star marks signal at the MT plus end. Movie S4 Movie S4 Single molecule experiments revealing the residence of INT1-SNAP-Atto-488, INT2-SNAP-Atto-488 single, INT1+2-SNAP-Atto-488 at MT plus ends. Left, Representative movies of INT1-SNAP-Atto-488 tracking dynamic MTs.. Middle, representative movies of INT2-SNAP-Atto-488 tracking dynamic MTs. Right, representative movies of INT1+2-SNAP-Atto-488 tracking dynamic MTs. Star marks signal at the MT plus end.

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Journal Details

This article was published in the following journal.

Name: Molecular biology of the cell
ISSN: 1939-4586
Pages: mbcE19020093

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Medical and Biotech [MESH] Definitions

A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. The enzyme functions in the nucleolar structure and transcribes DNA into RNA. It has different requirements for cations and salts than RNA polymerase II and III and is not inhibited by alpha-amanitin. EC 2.7.7.6.

A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.

A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure where it transcribes DNA into RNA. It has specific requirements for cations and salt and has shown an intermediate sensitivity to alpha-amanitin in comparison to RNA polymerase I and II. EC 2.7.7.6.

A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II. EC 2.7.7.7.

A DNA-directed DNA polymerase that functions in the replication of MITOCHONDRIAL DNA. Mutations in the gene that encodes this enzyme (POLG) are associated with some forms of OPHTHALMOPLEGIA, CHRONIC EXTERNAL PROGRESSIVE.

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