Computational investigation of IP 3 diffusion.

Autor: Ornelas-Guevara R; Unité de Chronobiologie Théorique, Faculté Des Sciences, Université Libre de Bruxelles (ULB), Boulevard du Triomphe, CP231, Brussels, Belgium., Gil D; The Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany., Voorsluijs V; Luxembourg Centre for Systems Biomedecine, Université du Luxembourg, Esch-sur-Alzette, Luxemburg., Dupont G; Unité de Chronobiologie Théorique, Faculté Des Sciences, Université Libre de Bruxelles (ULB), Boulevard du Triomphe, CP231, Brussels, Belgium. Genevieve.Dupont@ulb.be.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Feb 20; Vol. 13 (1), pp. 2922. Date of Electronic Publication: 2023 Feb 20.
DOI: 10.1038/s41598-023-29876-3
Abstrakt: Inositol 1,4,5-trisphosphate (IP 3 ) plays a key role in calcium signaling. After stimulation, it diffuses from the plasma membrane where it is produced to the endoplasmic reticulum where its receptors are localized. Based on in vitro measurements, IP 3 was long thought to be a global messenger characterized by a diffusion coefficient of ~ 280 μm 2 s -1 . However, in vivo observations revealed that this value does not match with the timing of localized Ca 2+ increases induced by the confined release of a non-metabolizable IP 3 analog. A theoretical analysis of these data concluded that in intact cells diffusion of IP 3 is strongly hindered, leading to a 30-fold reduction of the diffusion coefficient. Here, we performed a new computational analysis of the same observations using a stochastic model of Ca 2+ puffs. Our simulations concluded that the value of the effective IP 3 diffusion coefficient is close to 100 μm 2 s -1 . Such moderate reduction with respect to in vitro estimations quantitatively agrees with a buffering effect by non-fully bound inactive IP 3 receptors. The model also reveals that IP 3 spreading is not much affected by the endoplasmic reticulum, which represents an obstacle to the free displacement of molecules, but can be significantly increased in cells displaying elongated, 1-dimensional like geometries.
(© 2023. The Author(s).)
Databáze: MEDLINE
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