G-protein βγ subunits translocate reversibly from the plasma membrane to internal membranes on receptor activation. Translocation rates differ depending on the γ subunit type. There is limited understanding of the role of the differential rates of Gβγ translocation in modulating signaling dynamics in a cell. Bifurcation analysis of the calcium oscillatory network structure predicts that the translocation rate of a signaling protein can regulate the damping of system oscillation. Here, we examined whether the Gβγ translocation rate regulates calcium oscillations induced by G-protein-coupled receptor activation. Oscillations in HeLa cells expressing γ subunit types with different translocation rates were imaged and quantitated. The results show that differential Gβγ translocation rates can underlie the diversity in damping characteristics of calcium oscillations among cells. Mathematical modeling shows that a translocation embedded motif regulates damping of G-protein-mediated calcium oscillations consistent with experimental data. The current study indicates that such a motif may act as a tuning mechanism to design oscillations with varying damping patterns by using intracellular translocation of a signaling component.
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http://dx.doi.org/10.1016/j.bpj.2014.05.020 | DOI Listing |
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Department of Neurophysiology, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Mexico City, Mexico.
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January 2025
Northeastern University, Department of Bioengineering, Boston, Massachusetts, United States.
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Adv Sci (Weinh)
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Clinical Research Center, Postdoctoral Station of Clinical Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, P. R. China.
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Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, 610065, Sichuan University, Chengdu, P.R. China.
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View Article and Find Full Text PDFProtein Sci
February 2025
Department of Physics, University of Washington, Seattle, Washington, USA.
Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes.
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