Oscillatory dynamics and their modulation are crucial for cellular decision-making; however, analysing these dynamics remains challenging. Here, we present a tool that combines the light-activated adenylate cyclase mPAC with the cAMP biosensor Pink Flamindo, enabling precise manipulation and real-time monitoring of cAMP oscillation frequencies in Dictyostelium. High-frequency modulation of cAMP oscillations induced cell aggregation and multicellular formation, even at low cell densities, such as a few dozen cells. At the population level, chemotactic aggregation is driven by modulated frequency signals. Additionally, modulation of cAMP frequency significantly reduced the amplitude of the shuttling behaviour of the transcription factor GtaC, demonstrating low-pass filter characteristics capable of converting subtle oscillation changes, such as from 6 min to 4 min, into gene expression. These findings enhance our understanding of frequency-selective cellular decoding and its role in cellular signalling and development.
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http://dx.doi.org/10.1242/dev.204403 | DOI Listing |
Development
January 2025
Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Oscillatory dynamics and their modulation are crucial for cellular decision-making; however, analysing these dynamics remains challenging. Here, we present a tool that combines the light-activated adenylate cyclase mPAC with the cAMP biosensor Pink Flamindo, enabling precise manipulation and real-time monitoring of cAMP oscillation frequencies in Dictyostelium. High-frequency modulation of cAMP oscillations induced cell aggregation and multicellular formation, even at low cell densities, such as a few dozen cells.
View Article and Find Full Text PDFDev Cell
December 2024
Centre for Life's Origins and Evolution, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK. Electronic address:
Oscillatory phenomena play widespread roles in the control of biological systems. In D. discoideum, oscillatory cyclic adenosine monophosphate (cAMP) signaling drives collective behavior and induces a temporal developmental gene expression program.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Unlabelled: N-methyl-D-aspartate receptors (NMDARs) comprise a family of ligand-gated ionotropic glutamate receptors that mediate a slow, calcium-permeable component to excitatory neurotransmission. The GluN2D subunit is enriched in GABAergic inhibitory interneurons in cortical tissue. Diminished levels of GABAergic inhibition contribute to multiple neuropsychiatric conditions, suggesting that enhancing inhibition may have therapeutic utility, thus making GluN2D modulation an attractive drug target.
View Article and Find Full Text PDFPLoS Comput Biol
October 2024
Department of Pharmacology, University of California San Diego, San Diego, California, United States of America.
The nanoscale organization of enzymes associated with the dynamics of second messengers is critical for ensuring compartmentation and localization of signaling molecules in cells. Specifically, the spatiotemporal orchestration of cAMP and Ca2+ oscillations is critical for many cellular functions. Previous experimental studies have shown that the formation of nanodomains of A-kinase anchoring protein 79/150 (AKAP150) and adenylyl cyclase 8 (AC8) on the surface of pancreatic MIN6 β cells modulates the phase of Ca2+-cAMP oscillations from out-of-phase to in-phase.
View Article and Find Full Text PDFTransl Psychiatry
October 2024
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 100191, Beijing, China.
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