Circadian oscillation in primary cilium length by clock genes regulates fibroblast cell migration

Abstract

Various mammalian cells have autonomous cellular clocks that are produced by the transcriptional cycle of clock genes. Cellular clocks provide circadian rhythms for cellular functions via transcriptional and cytoskeletal regulation. The vast majority of mammalian cells possess a primary cilium, an organelle protruding from the cell surface. Here, we investigated the little‐known relationship between circadian rhythm and primary cilia. The length and number of primary cilia showed circadian dynamics both in vitro and in vivo. The circadian rhythm of primary cilium length was abolished by SR9011 and Bmal1 knockout. A centrosomal protein, pericentrin, transiently accumulates in centriolar satellites, the base of primary cilia at the shortest cilia phase, and induces elongation of primary cilia at the longest cilia phase in the circadian rhythm of primary cilia. In addition, rhythmic cell migration during wound healing depends on the length of primary cilia and affects the rate of wound healing. Our findings demonstrate that the circadian dynamics of primary cilium length by clock genes control fibroblast migration and could provide new insights into chronobiology.

Systemic migrations in enucleated cells

“…Temporal oscillations with a period close to 24h have also been associated with cell migration. For instance, circadian rhythms shaping the concentration of adhesion molecules and of the chemokine CCL21 (Holtkamp et al, 2021), oscillations in intracellular pericentrin protein levels (Nakazato et al, 2023), and daily rhythms in the concentration of actin cytoskeleton regulatory molecules (Hoyle et al, 2017). Spatiotemporal waves examples include intracellular Ca 2+ waves (Rondé et al, 2000; Takayama and Onami, 2016), actin waves (Vicker, 2002; Asano et al, 2008; Stankevicins et al, 2020), PIP3 waves (Asano et al, 2008), NAD(P)H waves (Kindzelskii et al, 1998; Kindzelskii and Petty, 2002), and kinase waves (Aoki et al, 2017; Aikin et al, 2020).…”

Excessive F-Actin and Microtubule Formation Mediates Primary Cilia Shortening and Loss in Response to Increased Extracellular Osmotic Pressure

“…Ciliogenesis occurs during the non-dividing phase of the cell cycle, while ciliary resorption occurs under the mitotic phase (Plotnikova et al, 2009). Cell-intrinsic circadian rhythms also regulate ciliary elongation and resorption (Tu et al, 2023; Nakazato et al, 2023a). Resorption of primary cilia occurs in response to some stimulation as well.…”