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Comments on Peel, Nina et al. (2013) International Worm Meeting "Centriole Copy Number Control Is Mediated by Protein Phosphatase 1-Beta in C. elegans." (0)
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Peel, Nina, Iyer, Jyoti, Dougherty, Michael, & O'Connell, Kevin (2013). Centriole Copy Number Control Is Mediated by Protein Phosphatase 1-Beta in C. elegans presented in International Worm Meeting. Unpublished information; cite only with author permission.
Centrioles are small cylindrical structures that play essential roles during cell division and development. In mitotic cells, centrioles direct formation of centrosomes, microtubule-organizing centers that promote bipolar spindle formation. In post-mitotic cells, centrioles serve as basal bodies to nucleate the formation of cilia and flagella. Under control of the kinase ZYG-1, centrioles duplicate precisely once per cell cycle with one daughter centriole assembled next to each pre-existing mother centriole. The fidelity of this process is essential for the proper segregation of chromosomes, as too few or too many centrioles lead to the formation of mono- or multipolar spindles. While defects in centriole number control have been linked to cancer and other diseases, the mechanisms that constrain centriole assembly to one daughter per mother are poorly understood. We have found that loss-of-function mutations that affect either of two highly conserved PP1 regulators (referred to here as I-2 and SDS-22) can suppress the centriole duplication defect incurred by partial loss of ZYG-1 activity. Likewise, reduced expression of GSP-1, the worm PP1-beta catalytic subunit also suppresses a zyg-1 mutant. Proteomic analysis indicates that both I-2 and SDS-22 bind GSP-1, but function in distinct PP1 complexes. Significantly, we find that loss of PP1-beta activity leads to the over-expression of ZYG-1, suggesting a likely mechanism of suppression. Most interestingly, in a zyg-1(+) background, strong inhibition of I-2 or SDS-22 activity leads to centriole over-duplication whereby mother centrioles produce more than a single daughter. Our results show that by limiting ZYG-1 expression, PP1-beta acts as a key determinant of centriole number.
Affiliations:
- Department of Biology, The College of New Jersey, Ewing, NJ 08628
- Laboratory of Biochemistry & Genetics, NIDDK, NIH, Bethesda, MD 20892