Here, we address the regulation of microtubule nucleation during interphase by genetically ablating one, or two, of three major mammalian γ‐TuRC‐binding factors namely pericentrin, CDK5Rap2, and AKAP450. Unexpectedly, we find that while all of th...
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https://www.riss.kr/link?id=O90206070
2018년
-
1469-221X
1469-3178
SCI;SCIE;SCOPUS
학술저널
n/a-n/a [※수록면이 p5 이하이면, Review, Columns, Editor's Note, Abstract 등일 경우가 있습니다.]
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
Here, we address the regulation of microtubule nucleation during interphase by genetically ablating one, or two, of three major mammalian γ‐TuRC‐binding factors namely pericentrin, CDK5Rap2, and AKAP450. Unexpectedly, we find that while all of th...
Here, we address the regulation of microtubule nucleation during interphase by genetically ablating one, or two, of three major mammalian γ‐TuRC‐binding factors namely pericentrin, CDK5Rap2, and AKAP450. Unexpectedly, we find that while all of them participate in microtubule nucleation at the Golgi apparatus, they only modestly contribute at the centrosome where CEP192 has a more predominant function. We also show that inhibiting microtubule nucleation at the Golgi does not affect centrosomal activity, whereas manipulating the number of centrosomes with centrinone modifies microtubule nucleation activity of the Golgi apparatus. In centrosome‐free cells, inhibition of Golgi‐based microtubule nucleation triggers pericentrin‐dependent formation of cytoplasmic‐nucleating structures. Further depletion of pericentrin under these conditions leads to the generation of individual microtubules in a γ‐tubulin‐dependent manner. In all cases, a conspicuous MT network forms. Strikingly, centrosome loss increases microtubule number independently of where they were growing from. Our results lead to an unexpected view of the interphase centrosome that would control microtubule network organization not only by nucleating microtubules, but also by modulating the activity of alternative microtubule‐organizing centers.
During interphase, microtubules can be generated from a variety of microtubule‐organizing centers (MTOCs) the activity of which is regulated in a hierarchical manner. The centrosome (CTR) controls Golgi apparatus (GA) activity, and both of them inhibit MT nucleation from cytoplasmic aggregates (cMTOCs). When all MTOCs are inactive, individual MTs can still form in a γ‐tubulin dependent manner.
Canonical γ‐TuRC receptors are essential for Golgi and cytoplasmic MT nucleation but they are dispensable for the centrosome that employs additional mechanisms.
The centrosome negatively regulates alternative MTOCs, thereby limiting the total number of MTs during interphase.
The activity of microtubule‐organizing centers during interphase is regulated in a hierarchical manner. The centrosome controls Golgi apparatus activity, and both of them inhibit γ‐tubulin‐dependent MT nucleation from cytoplasmic aggregates.
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