ArticlePLoS computational biology2024
Spatiotemporal orchestration of calcium-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop.
Article in PLoS computational biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- Mechanochemical modeling of exercise-induced skeletal muscle hypertrophy.PLoS computational biology · 2026Article
- Red-Shifted Epac-Based FRET cAMP Sensors for All-Optical cAMP Control and Multiparameter Imaging.Cells · 2026Article
- Adenosine Signaling in Primary and Metastatic Brain Tumors: Immune Suppression, Tumor Progression, and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Dynamics of the formation of flat clathrin lattices in response to growth factor stimulus.PLoS computational biology · 2026Article
- Recent advances in spying on cell signaling with fluorescent biosensors.Current opinion in cell biology · 2025Review
- Dynamics of the formation of flat clathrin lattices in response to growth factor stimulus.bioRxiv : the preprint server for biology · 2025Article
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Abstract
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. In this work, we develop computational models of the Ca2+/cAMP pathway and AKAP/AC nanodomain formation that give rise to the two important predictions: instead of an arbitrary phase difference, the out-of-phase Ca2+/cAMP oscillation reaches Ca2+ trough and cAMP peak simultaneously, which is defined as inversely out-of-phase; the in-phase and inversely out-of-phase oscillations associated with Ca2+-cAMP dynamics on and away from the nanodomains can be explained by an incoherent feedforward loop. Factors such as cellular surface-to-volume ratio, compartment size, and distance between nanodomains do not affect the existence of in-phase or inversely out-of-phase Ca2+/cAMP oscillation, but cellular surface-to-volume ratio and compartment size can affect the time delay for the inversely out-of-phase Ca2+/cAMP oscillation while the distance between two nanodomains does not. Finally, we predict that both the Turing pattern-generated nanodomains and experimentally measured nanodomains demonstrate the existence of in-phase and inversely out-of-phase Ca2+/cAMP oscillation when the AC8 is at a low level, consistent with the behavior of an incoherent feedforward loop. These findings unveil the key circuit motif that governs cAMP and Ca2+ oscillations and advance our understanding of how nanodomains can lead to spatial compartmentation of second messengers.
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