A two-step mechanism for the inactivation of microtubule organizing center function at the centrosome

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Abstract

The centrosome acts as a microtubule organizing center (MTOC), orchestrating microtubules into the mitotic spindle through its pericentriolar material (PCM). This activity is biphasic, cycling through assembly and disassembly during the cell cycle. Although hyperactive centrosomal MTOC activity is a hallmark of some cancers, little is known about how the centrosome is inactivated as an MTOC. Analysis of endogenous PCM proteins in C. elegans revealed that the PCM is composed of partially overlapping territories organized into an inner and outer sphere that are removed from the centrosome at different rates and using different behaviors. We found that phosphatases oppose the addition of PCM by mitotic kinases, ultimately catalyzing the dissolution of inner sphere PCM proteins at the end of mitosis. The nature of the PCM appears to change such that the remaining aging PCM outer sphere is mechanically ruptured by cortical pulling forces, ultimately inactivating MTOC function at the centrosome.

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Data generated or analyzed during this study are included in the manuscript and supporting files.

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Jérémy Magescas

Department of Biology, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7832-0851
Jenny C Zonka

Department of Biology, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Jessica L Feldman

Department of Biology, Stanford University, Stanford, United States

For correspondence
feldmanj@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5210-5045

Funding

March of Dimes Foundation (Basil O'Connor Starter Scholar Research Award)

Jessica L Feldman

National Institutes of Health (DP2GM119136-01)

Jessica L Feldman

American Heart Association (Postdoctoral Fellowship)

Jérémy Magescas

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.