Person:

Zwicker, David

ABSTRACT Centrosomes are major microtubule-organizing centers composed of centrioles surrounded by an extensive proteinacious layer called the pericentriolar material (PCM). In Caenorhabditis elegans embryos, the mitotic PCM expands by Polo-like kinase 1 (PLK-1) phosphorylation-accelerated assembly of SPD-5 molecules into supramolecular scaffolds. However, how PLK-1 phosphorylation regulates SPD-5 assembly is not known. We found that a mutant version of SPD-5 that is insensitive to PLK-1 phosphorylation (SPD-54A) could localize to PCM but was unable to rescue the reduction in PCM size and density when wild-type SPD-5 levels were decreased. In vitro, purified SPD-54A self-assembled into functional supramolecular scaffolds over long time scales, suggesting that phosphorylation only controls the rate of SPD-5 scaffold assembly. Furthermore, the SPD-5 scaffold, once assembled, remained intact and supported microtubule nucleation in the absence of PLK-1 activity in vivo. We conclude that PLK-1 is required for rapid assembly of the PCM scaffold but not for scaffold maintenance or function. Based on this idea, we developed a theoretical model that adequately predicted PCM growth rates in different mutant conditions in vivo. We propose that PLK-1 phosphorylation-dependent conversion of SPD-5 into an assembly-competent form underlies PCM formation in vivo and that the rate of this conversion determines final PCM size and density.

The olfactory system removes correlations in natural odors using a network of inhibitory neurons in the olfactory bulb. It has been proposed that this network integrates the response from all olfactory receptors and inhibits them equally. However, how such global inhibition influences the neural representations of odors is unclear. Here, we study a simple statistical model of the processing in the olfactory bulb, which leads to concentration-invariant, sparse representations of the odor composition. We show that the inhibition strength can be tuned to obtain sparse representations that are still useful to discriminate odors that vary in relative concentration, size, and composition. The model reveals two generic consequences of global inhibition: (i) odors with many molecular species are more difficult to discriminate and (ii) receptor arrays with heterogeneous sensitivities perform badly. Comparing these predictions to experiments will help us to understand the role of global inhibition in shaping normalized odor representations in the olfactory bulb.