4.8 Article

Microtubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG

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NATURE COMMUNICATIONS
卷 14, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-023-35955-w

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In human cells, the microtubule polymerase ch-TOG promotes nucleation of microtubules at the interphase centrosome and the Golgi by transiently interacting with the microtubule nucleator gamma TuRC. This mechanism allows for the regulation of microtubule arrays organization.
Organization of microtubule arrays requires spatio-temporal regulation of the microtubule nucleator gamma-tubulin ring complex (gamma TuRC) at microtubule organizing centers (MTOCs). MTOC-localized adapter proteins are thought to recruit and activate gamma TuRC, but the molecular underpinnings remain obscure. Here we show that at interphase centrosomes, rather than adapters, the microtubule polymerase ch-TOG (also named chTOG or CKAP5) ultimately controls gamma TuRC recruitment and activation. ch-TOG co-assembles with gamma TuRC to stimulate nucleation around centrioles. In the absence of ch-TOG, gamma TuRC fails to localize to these sites, but not the centriole lumen. However, whereas some ch-TOG is stably bound at subdistal appendages, it only transiently associates with PCM. ch-TOG's dynamic behavior requires its tubulin-binding TOG domains and a C-terminal region involved in localization. In addition, ch-TOG also promotes nucleation from the Golgi. Thus, at interphase centrosomes stimulation of nucleation and gamma TuRC attachment are mechanistically coupled through transient recruitment of ch-TOG, and ch-TOG's nucleation-promoting activity is not restricted to centrosomes. The molecular mechanisms underpinning the organization of microtubule arrays remain unclear. Here the authors show that in human cells, the microtubule polymerase ch-TOG promotes nucleation of microtubules at the interphase centrosome and the Golgi through a mechanism that involves transient interaction with the microtubule nucleator gamma TuRC.

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