Université de Fribourg

Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

Brenna, Andrea ; Olejniczak, Iwona ; Chavan, Rohit ; Ripperger, Jürgen A ; Langmesser, Sonja ; Cameroni, Elisabetta ; Hu, Zehan ; De Virgilio, Claudio ; Dengjel, Jörn ; Albrecht, Urs

In: eLife, 2019, vol. 8, p. e50925

Circadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here, we show that the cyclin-dependent kinase 5...

Université de Fribourg

Medicine in the fourth dimension

R.Cederroth, Christopher ; Albrecht, Urs ; Bass, Joseph ; Brown, Steven A. ; Dyhrfjeld-Johnsen, Jonas ; Gachon, Frederic ; Green, Carla B. ; Hastings, Michael H. ; Helfrich-Förster, Charlotte ; B.Hogenesch, John ; Lévi, Francis ; Loudon, Andrew ; B.Lundkvist, Gabriella ; H.Meijer, Johanna ; Rosbash, Michael ; S.Takahashi, Joseph ; Young, Michael ; Canlon, Barbara

In: Cell Metabolism, 2019, vol. 30, no. 2, p. 238–250

The importance of circadian biology has rarely been considered in pre-clinical studies, and even more when translating to the bedside. Circadian biology is becoming a critical factor for improving drug efficacy and diminishing drug toxicity. Indeed, there is emerging evidence showing that some drugs are more effective at nighttime than daytime, whereas for others it is the opposite. This...

Université de Fribourg

Circadian clocks and sleep: impact of rhythmic metabolism and waste clearance on the brain

Albrecht, Urs ; Ripperger, Jürgen A.

In: Trends in Neurosciences, 2018, vol. 41, no. 10, p. 677–688

The rotation of the Earth around its axis causes periodic exposure of half of its surface to sunlight. This daily recurring event has been internalized in most organisms in the form of cellular circadian clock mechanisms. These cellular clocks are synchronized with each other in various ways to establish circadian networks that build the circadian program in tissues and organs, coordinating...

Consortium of Swiss Academic Libraries

Circadian rhythms and sleep—the metabolic connection

Albrecht, Urs

In: Pflügers Archiv - European Journal of Physiology, 2012, vol. 463, no. 1, p. 23-30

Université de Fribourg

Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics

Schmitt, Karen ; Grimm, Amandine ; Dallmann, Robert ; Oettinghaus, Bjoern ; Restelli, Lisa Michelle ; Witzig, Melissa ; Ishihara, Naotada ; Mihara, Katsuyoshi ; Ripperger, Jürgen A. ; Albrecht, Urs ; Frank, Stephan ; Brown, Steven A. ; Eckert, Anne

In: Cell Metabolism, 2018, vol. 27, no. 3, p. 657-666.e5

Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vitro and in vivo models, including human skin...

Université de Fribourg

VGLUT1 binding to endophilin or intersectin1 and dynamin phosphorylation in a diurnal context

Richter, Karin ; Schmutz, Isabelle ; Darna, Mahesh ; Zander, Johannes-F ; Chavan, Rohit ; Albrecht, Urs ; Ahnert-Hilger, Gudrun

In: Neuroscience, 2018, vol. 371, p. 29–37

Glutamate is concentrated into synaptic vesicles (SV) by the vesicular glutamate transporters (VGLUT) 1 and 2. VGLUTs also harbor a Na+/Pi-transport activity when residing at the plasma membrane. Here we aimed to identify whether the diurnal switches of VGLUT1 parallels interactions with or modification of endocytic proteins.VGLUT1 and dynamin bind to SH3 domains of either endophilin (Enph)...

Université de Fribourg

Disturbed processing of contextual information in HCN3 channel deficient mice

Stieglitz, Marc S. ; Fenske, Stefanie ; Hammelmann, Verena ; Becirovic, Elvir ; Schöttle, Verena ; Delorme, James E. ; Schöll-Weidinger, Martha ; Mader, Robert ; Deussing, Jan ; Wolfer, David P. ; Seeliger, Mathias W. ; Albrecht, Urs ; Wotjak, Carsten T. ; Biel, Martin ; Michalakis, Stylianos ; Wahl-Schott, Christian

In: Frontiers in Molecular Neuroscience, 2018, vol. 10, p. -

Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) in the nervous system are implicated in a variety of neuronal functions including learning and memory, regulation of vigilance states and pain. Dysfunctions or genetic loss of these channels have been shown to cause human diseases such as epilepsy, depression, schizophrenia, and Parkinson's disease. The physiological...

Université de Fribourg

REV-ERBα regulates Fgf21 expression in the liver via hepatic nuclear factor 6

Chavan, Rohit ; Preitner, Nadia ; Okabe, Takashi ; Mansencal Strittmatter, Laureen ; Xu, Cheng ; Ripperger, Jürgen A. ; Pitteloud, Nelly ; Albrecht, Urs

In: Biology Open, 2017, vol. 6, no. 1, p. 1–7

The circadian clock contributes to the timing of many body functions including metabolism and reproduction. The hepatokine fibroblast growth factor 21 (FGF21) is a critical metabolic regulator involved in modulation of fertility. Here we show that lack of the clock component REV-ERBα elevates FGF21 levels in liver and plasma. At the molecular level, REV-ERBα modulates the expression of...

Université de Fribourg

Rev‐erbα modulates the hypothalamic orexinergic system to influence pleasurable feeding behaviour in mice

Feillet, Céline A. ; Bainier, Claire ; Mateo, Maria ; Blancas-Velázquez, Aurea ; Salaberry, Nora L. ; Ripperger, Jürgen A. ; Albrecht, Urs ; Mendoza, Jorge

In: Addiction Biology, 2017, vol. 22, no. 2, p. 411–422

The drive to eat is regulated by two compensatory brain pathways termed as homeostatic and hedonic. Hypothalamic orexinergic (ORX) neurons regulate metabolism, feeding and reward, thus controlling physiological and hedonic appetite. Circadian regulation of feeding, metabolism and rhythmic activity of ORX cells are driven by the brain suprachiasmatic clock. How the circadian clock impacts on...