A positive feedback loop drives centrosome maturation in flies

Abstract

Centrosomes are formed when mother centrioles recruit pericentriolar material (PCM) around themselves. The PCM expands dramatically as cells prepare to enter mitosis (a process termed centrosome maturation), but it is unclear how this expansion is achieved. In flies, Spd-2 and Cnn form an extensive scaffold around the mother centriole that recruits other components of the mitotic PCM, and the Polodependent phosphorylation of Cnn at the centrosome is crucial for scaffold assembly.Here we show that, like Cnn, Spd-2 is specifically phosphorylated at centrosomes. This phosphorylation appears to create multiple phosphorylated S-S/T(p) motifs that allow Spd-2 to recruit Polo to the expanding scaffold. If Spd-2 cannot recruit Polo to the expanding scaffold, the scaffold is initially assembled around the mother centriole, but it cannot expand outwards, and centrosome maturation fails. We conclude that Spd-2, Polo and Cnn cooperate to form a positive feedback loop that drives the dramatic expansion of the mitotic centrosome in flies.

Differential Requirements for Centrioles in Mitotic Centrosome Growth and Maintenance

“…By acute inactivation, we found SPD-2 to be required for PCM expansion in vivo, though not for maintenance of the PCM scaffold polymer once recruited. One attractive model put forward in Drosophila is that SPD-2 specifically incorporates at centrioles and then 'fluxes' outwards as the PCM expands (Alvarez Rodrigo et al, 2018;Conduit et al, 2014). The apparent absence of SPD-2 flux in C. elegans leads us to suggest a revised version, whereby SPD-2 recruits PLK-1 to centrioles.…”

“…Centrioles, therefore, do not directly participate in PCM expansion by acting as docking sites for new scaffold protein incorporation. However, this does not exclude an indirect, signaling role, perhaps mediated by SPD-2 and PLK-1 (Alvarez Rodrigo et al, 2018). Mathematical modeling of centrosome dynamics in the C. elegans embryo argues that the observed kinetics of PCM growth can be explained by autocatalytic assembly coupled with a degree of catalytic activity of the centrioles suppressing the unequal growth of the two centrosomes (Zwicker et al, 2014).…”

PCMD-1 Organizes Centrosome Matrix Assembly in C. elegans

“…Similar to worms, in flies, the Polo, Spd-2, and CNN module is recruited to the centrosome during interphase [1]. As cells prepare to enter mitosis, activated Polo phosphorylates Spd-2 and CNN, thereby establishing a positive feedback loop, which drives rapid PCM growth [7,34].…”

A free-running oscillator times and executes centriole biogenesis

“…Among these models, Lorentzian best fit the data ( Figure S1D), so all the discrete Plk4 oscillation curves in S-phase were regressed using this function. The Lorentzian and Gaussian functions are described in Prism 7, while the latter two functions are in-house algorithms (Alvarez Rodrigo et al, 2018).…”