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.
Highlights
Numerous cell functions such as transport, migration, and division are achieved through the specific spatial organization of microtubules imparted by microtubule organizing centers (MTOCs)
We find that C. elegans pericentriolar material (PCM) is composed of overlapping spheres of proteins similar to what has been observed in other systems, with SPD-5 and g-tubulin ring complex (g-TuRC) occupying distinct regions from known binding partners SPD-2 and MZT-1, respectively
We assessed the localization of the centriole component SAS-4, the PCM scaffolding proteins SPD-2 and SPD-5, the g-TuRC components GIP-1 and MZT-1, the mitotic kinases AIR-1 and PLK-1, and the microtubule associated proteins ZYG-9, TAC-1 and TPXL-1 (Figure 1B, Figure 1—figure supplement 1)
Summary
Numerous cell functions such as transport, migration, and division are achieved through the specific spatial organization of microtubules imparted by microtubule organizing centers (MTOCs). In Drosophila and human cell lines, PCM proteins including a subset of scaffolding proteins are organized in cumulative layers recruiting microtubule nucleation and organization factors, such as the conserved microtubule nucleating g-tubulin ring complex (g-TuRC) (Fu and Glover, 2012; Lawo et al, 2012; Mennella et al, 2012). Together with the highly conserved kinase AIR-1/Aurora-A, SPD-2 and SPD-5 are required to localize g-TuRC, which in C. elegans is composed of TBG-1/g-tubulin, GIP-1/GCP3, GIP-2/GCP2 and MZT-1/MZT1 (Bobinnec et al, 2000; Hamill et al, 2002; Hannak et al, 2002; Kemp et al, 2004; Lin et al, 2015; Oakley et al, 2015; Sallee et al, 2018). The major role of the g-TuRC at the PCM in C. elegans might be to anchor microtubules at the periphery as loss of g-TuRC results in microtubules distributed throughout the PCM (O’Toole et al, 2012)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
