Centrosome Function: Sometimes Less Is More

Abstract

Tight regulation of centrosome duplication is critical to ensure that centrosome number doubles once and only once per cell cycle. Superimposed onto this centrosome duplication cycle is a functional centrosome cycle in which they alternate between phases of quiescence and robust microtubule (MT) nucleation and MT‐anchoring activities. In vertebrate cycling cells, interphase centrioles accumulate less pericentriolar material (PCM), reducing their MT nucleation capacity. In mitosis, centrosomes mature, accumulating more PCM to increase their nucleation and anchoring capacities to form robust MT asters. Interestingly, functional cycles of centrosomes can be altered to suit the cell’s needs. Some interphase centrosomes function as a microtubule‐organizing center by increasing their ability to anchor MTs to form centrosomal radial arrays. Other interphase centrosomes maintain their MT nucleation capacity but reduce/eliminate their MT‐anchoring capacity. Recent work demonstrates that Drosophila cells take this to the extreme, whereby centrioles lose all detectable PCM during interphase, offering an explanation as to how centrosome‐deficient flies develop to adulthood. Drosophila stem cells further modify the functional cycle by differentially regulating their two centrioles – a situation that seems important for stem cell asymmetric divisions, as misregulation of centrosome duplication in stem/progenitor cells can promote tumor formation. Here, we review recent findings that describe variations in the functional cycle of centrosomes.

Cortical Microtubule Arrays Are Initiated from a Nonrandom Prepattern Driven by Atypical Microtubule Initiation

“…While most microtubules are nucleated by g-TuRCs (Teixidó-Travesa et al, 2012), nucleation has also been found to be facilitated by several microtubule plus end-binding proteins (Rogers et al, 2008;Rusan and Rogers, 2009) S7). The noncanonical microtubule initiations we describe in this article are most likely not derived from g-TuRC complexes because of the absence of GCP2-3xGPF marker at the cell cortex during the disassembly phase, suggesting that another factor may serve as the nucleator or that initiations may arise from stabilized short fragments of microtubules.…”

Cep57, a NEDD1-binding pericentriolar material component, is essential for spindle pole integrity

“…Depletion of Cep57 could therefore cause spindle microtubule disorganization and PCM instability, which would cause some PCMs to be pulled out by microtubule-mediated forces. Those PCM fragments do not contain centrioles but are able to recruit other PCM components and nucleate microtubules [35], eventually forming new spindle poles.…”

TIG3 Interaction at the Centrosome Alters Microtubule Distribution and Centrosome Function

“…The PCM includes hundreds of proteins, including many large scaffold proteins that function as regulatory-protein docking sites (Doxsey et al, 2005), and the ctubulin ring complexes that are responsible for microtubule nucleation (Doxsey et al, 2005;Kreitzer et al, 1999). The centrosome and the microtubule system are intimately connected, and deficiencies in either microtubule or centrosome function can reduce cell survival (Mazzorana et al, 2011;Rusan and Rogers, 2009). Moreover, because the centrosome and microtubules reciprocally influence the function of each other, we studied the impact of TIG3 on both the centrosome and the microtubules.…”