bims-ciryme 2024-08-18 papers

Issue of 2024‒08‒18
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham

Proc Natl Acad Sci U S A. 2024 Aug 20. 121(34): e2404738121

Circadian period is compensated for repressor protein turnover rates in single cells.

Christian H Gabriel, Marta Del Olmo, Arunya Rizki Widini, Rashin Roshanbin, Jonas Woyde, Ebrahim Hamza, Nica-Nicoleta Gutu, Amin Zehtabian, Helge Ewers, Adrian Granada, Hanspeter Herzel, Achim Kramer.

Most mammalian cells have molecular circadian clocks that generate widespread rhythms in transcript and protein abundance. While circadian clocks are robust to fluctuations in the cellular environment, little is known about the mechanisms by which the circadian period compensates for fluctuating metabolic states. Here, we exploit the heterogeneity of single cells both in circadian period and a metabolic parameter-protein stability-to study their interdependence without the need for genetic manipulation. We generated cells expressing key circadian proteins (CRYPTOCHROME1/2 (CRY1/2) and PERIOD1/2 (PER1/2)) as endogenous fusions with fluorescent proteins and simultaneously monitored circadian rhythms and degradation in thousands of single cells. We found that the circadian period compensates for fluctuations in the turnover rates of circadian repressor proteins and uncovered possible mechanisms using a mathematical model. In addition, the stabilities of the repressor proteins are circadian phase dependent and correlate with the circadian period in a phase-dependent manner, in contrast to the prevailing model.

Keywords: circadian rhythms; fluorescence microscopy; metabolic compensation; protein degradation; single-cell imaging

DOI: https://doi.org/10.1073/pnas.2404738121

Curr Biol. 2024 Aug 05. pii: S0960-9822(24)00954-0. [Epub ahead of print]

Suprachiasmatic nucleus VIPergic fibers show a circadian rhythm of expansion and retraction.

Alexandra F Neitz, Bryn M Carter, M Fernanda Ceriani, Mark H Ellisman, Horacio O de la Iglesia.

In animals, overt circadian rhythms of physiology and behavior are centrally regulated by a circadian clock located in specific brain regions. In the fruit fly Drosophila and in mammals, these clocks rely on single-cell oscillators, but critical for their function as central circadian pacemakers are network properties that change dynamically throughout the circadian cycle as well as in response to environmental stimuli.1,2,3 In the fly, this plasticity involves circadian rhythms of expansion and retraction of clock neuron fibers.4,5,6,7,8,9,10,11,12,13,14 Whether these drastic structural changes are a universal property of central neuronal pacemakers is unknown. To address this question, we studied neurons of the mouse suprachiasmatic nucleus (SCN) that express vasoactive intestinal polypeptide (VIP), which are critical for the SCN to function as a central circadian pacemaker. By targeting the expression of the fluorescent protein tdTomato to these neurons and using tissue clearing techniques to visualize all SCN VIPergic neurons and their fibers, we show that, similar to clock neurons in the fly, VIPergic fibers undergo a daily rhythm of expansion and retraction, with maximal branching during the day. This rhythm is circadian, as it persists under constant environmental conditions and is present in both males and females. We propose that circadian structural remodeling of clock neurons represents a key feature of central circadian pacemakers that is likely critical to regulate network properties, the response to environmental stimuli, and the regulation of circadian outputs.

Keywords: circadian plasticity; circadian remodeling; neuronal plasticity; neuronal structural plasticity

DOI: https://doi.org/10.1016/j.cub.2024.07.051