Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action
Abstract
The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca2+-liberating second messenger inositol trisphosphate (IP3) diffuses with a coefficient (~280 μm2 s-1) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP3 is generally considered a “global” cellular messenger. We also reexamined this issue by measuring local IP3-evoked Ca2+ puffs to monitor IP3 diffusing from spot photorelease in neuroblastoma cells. Fitting these data by numerical simulations yielded a diffusion coefficient (≤10 μm2 s-1) about 30-fold slower than that previously reported. Here, we propose that diffusion of IP3 in mammalian cells is hindered by binding to immobile, functionally inactive receptors that were diluted in oocyte extracts. The predicted range of action of IP3 (<5 μm) is thus smaller than the size of typical mammalian cells, indicating that IP3 should better be considered as a local rather than a global cellular messenger.
- Authors:
-
- Univ. of California, Irvine, CA (United States). Dept.of Neurobiology and Behavior
- University of Buenos Aires (UBA), Buenos Aires (Argentina). Dept. of Physics
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
- Univ. of California, Irvine, CA (United States). Dept.of Neurobiology and Behavior, Dept. of Physiology and Biophysics
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH); Fund for Scientific and Technological Research (FONCyT)
- OSTI Identifier:
- 1411340
- Report Number(s):
- LA-UR-16-23743
Journal ID: ISSN 1945-0877; TRN: US1800210
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Science Signaling
- Additional Journal Information:
- Journal Volume: 9; Journal Issue: 453; Journal ID: ISSN 1945-0877
- Publisher:
- AAAS
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Biological Science; signaling, diffusion, inositol-triphosphate,1,4,5
Citation Formats
Dickinson, G. D., Ellefsen, K. L., Dawson, S. P., Pearson, J. E., and Parker, I. Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action. United States: N. p., 2016.
Web. doi:10.1126/scisignal.aag1625.
Dickinson, G. D., Ellefsen, K. L., Dawson, S. P., Pearson, J. E., & Parker, I. Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action. United States. https://doi.org/10.1126/scisignal.aag1625
Dickinson, G. D., Ellefsen, K. L., Dawson, S. P., Pearson, J. E., and Parker, I. Tue .
"Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action". United States. https://doi.org/10.1126/scisignal.aag1625. https://www.osti.gov/servlets/purl/1411340.
@article{osti_1411340,
title = {Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action},
author = {Dickinson, G. D. and Ellefsen, K. L. and Dawson, S. P. and Pearson, J. E. and Parker, I.},
abstractNote = {The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca2+-liberating second messenger inositol trisphosphate (IP3) diffuses with a coefficient (~280 μm2 s-1) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP3 is generally considered a “global” cellular messenger. We also reexamined this issue by measuring local IP3-evoked Ca2+ puffs to monitor IP3 diffusing from spot photorelease in neuroblastoma cells. Fitting these data by numerical simulations yielded a diffusion coefficient (≤10 μm2 s-1) about 30-fold slower than that previously reported. Here, we propose that diffusion of IP3 in mammalian cells is hindered by binding to immobile, functionally inactive receptors that were diluted in oocyte extracts. The predicted range of action of IP3 (<5 μm) is thus smaller than the size of typical mammalian cells, indicating that IP3 should better be considered as a local rather than a global cellular messenger.},
doi = {10.1126/scisignal.aag1625},
journal = {Science Signaling},
number = 453,
volume = 9,
place = {United States},
year = {Tue Nov 08 00:00:00 EST 2016},
month = {Tue Nov 08 00:00:00 EST 2016}
}
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Works referenced in this record:
Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites
journal, December 1998
- Finch, Elizabeth A.; Augustine, George J.
- Nature, Vol. 396, Issue 6713
Metabolism of Inositol 1,4,5-Trisphosphate and Inositol 1,3,4,5-Tetrakisphosphate by the Oocytes of Xenopus laevis
journal, February 1998
- Sims, Christopher E.; Allbritton, Nancy L.
- Journal of Biological Chemistry, Vol. 273, Issue 7
Inositol Trisphosphate Receptor Ca 2+ Release Channels
journal, April 2007
- Foskett, J. Kevin; White, Carl; Cheung, King-Ho
- Physiological Reviews, Vol. 87, Issue 2
IP 3 receptors: Take four IP 3 to open
journal, April 2016
- Taylor, Colin W.; Konieczny, Vera
- Science Signaling, Vol. 9, Issue 422
Twelve ways to look at a receptor: Receptors: Structure and Function, 2nd edn (A Practical Approach)
journal, November 2002
- Carlson, J. R.
- Journal of Cell Science, Vol. 115, Issue 21
Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate
journal, December 1992
- Allbritton, N.; Meyer, T.; Stryer, L.
- Science, Vol. 258, Issue 5089
Communication of Ca2+ signals via tunneling membrane nanotubes is mediated by transmission of inositol trisphosphate through gap junctions
journal, October 2016
- Lock, Jeffrey T.; Parker, Ian; Smith, Ian F.
- Cell Calcium, Vol. 60, Issue 4
Inositol 1,4,5-trisphosphate receptors in Xenopus laevis oocytes: Localization and modulation by Ca2+
journal, January 1994
- Callamaras, N.; Parker, I.
- Cell Calcium, Vol. 15, Issue 1
An algorithm for automated detection, localization and measurement of local calcium signals from camera-based imaging
journal, September 2014
- Ellefsen, Kyle L.; Settle, Brett; Parker, Ian
- Cell Calcium, Vol. 56, Issue 3
Quantal puffs of intracellular Ca2+ evoked by inositol trisphosphate in Xenopus oocytes.
journal, February 1995
- Yao, Y.; Choi, J.; Parker, I.
- The Journal of Physiology, Vol. 482, Issue 3
The lifetime of inositol 1,4,5-trisphosphate in single cells
journal, January 1995
- Wang, S. S.
- The Journal of General Physiology, Vol. 105, Issue 1
Spatial organization of intracellular Ca2+ signals
journal, April 2012
- Konieczny, Vera; Keebler, Michael V.; Taylor, Colin W.
- Seminars in Cell & Developmental Biology, Vol. 23, Issue 2
The Xenopus IP3 receptor: Structure, function, and localization in oocytes and eggs
journal, May 1993
- Kume, Shoen; Muto, Akira; Aruga, Jun
- Cell, Vol. 73, Issue 3
The Probability of Triggering Calcium Puffs Is Linearly Related to the Number of Inositol Trisphosphate Receptors in a Cluster
journal, April 2012
- Dickinson, George D.; Swaminathan, Divya; Parker, Ian
- Biophysical Journal, Vol. 102, Issue 8
Calcium-dependent Clustering of Inositol 1,4,5-Trisphosphate Receptors
journal, June 1998
- Wilson, Bridget S.; Pfeiffer, Janet R.; Smith, Alexander J.
- Molecular Biology of the Cell, Vol. 9, Issue 6, p. 1465-1478
Single-Molecule Tracking of Inositol Trisphosphate Receptors Reveals Different Motilities and Distributions
journal, August 2014
- Smith, Ian F.; Swaminathan, Divya; Dickinson, George D.
- Biophysical Journal, Vol. 107, Issue 4
Fire-diffuse-fire model of dynamics of intracellular calcium waves
journal, May 1999
- Dawson, S. P.; Keizer, J.; Pearson, J. E.
- Proceedings of the National Academy of Sciences, Vol. 96, Issue 11
Buffer Kinetics Shape the Spatiotemporal Patterns of IP 3 -Evoked Ca 2+ Signals
journal, December 2003
- Dargan, Sheila L.; Parker, Ian
- The Journal of Physiology, Vol. 553, Issue 3
Understanding calcium waves and sparks in central neurons
journal, February 2012
- Ross, William N.
- Nature Reviews Neuroscience, Vol. 13, Issue 3
Imaging the quantal substructure of single IP3R channel activity during Ca2+ puffs in intact mammalian cells
journal, March 2009
- Smith, I. F.; Parker, I.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 15
Pre-Steady-State Decoding of the Bicoid Morphogen Gradient
journal, February 2007
- Bergmann, Sven; Sandler, Oded; Sberro, Hila
- PLoS Biology, Vol. 5, Issue 2
Intercellular Ca 2+ Waves: Mechanisms and Function
journal, July 2012
- Leybaert, Luc; Sanderson, Michael J.
- Physiological Reviews, Vol. 92, Issue 3
Recording single-channel activity of inositol trisphosphate receptors in intact cells with a microscope, not a patch clamp
journal, July 2010
- Parker, Ian; Smith, Ian F.
- The Journal of General Physiology, Vol. 136, Issue 2
Binding of Inositol 1,4,5-trisphosphate (IP 3 ) and Adenophostin A to the N-Terminal region of the IP 3 Receptor: Thermodynamic Analysis Using Fluorescence Polarization with a Novel IP 3 Receptor Ligand
journal, March 2010
- Ding, Zhao; Rossi, Ana M.; Riley, Andrew M.
- Molecular Pharmacology, Vol. 77, Issue 6
Cell membrane permeable esters of d-myo-inositol 1,4,5-trisphosphate
journal, September 2007
- Dakin, Kenneth; Li, Wen-Hong
- Cell Calcium, Vol. 42, Issue 3
Diffusion coefficients of atp and creatine phosphate in isolated muscle: pulsed gradient31p nmr of small biological samples
journal, April 1995
- Hubley, Mark J.; Moerland, Timothy S.; Rosanske, Richard C.
- NMR in Biomedicine, Vol. 8, Issue 2
Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons
journal, January 2016
- Kruse, M.; Vivas, O.; Traynor-Kaplan, A.
- Journal of Neuroscience, Vol. 36, Issue 4
A Novel Postsynaptic Mechanism for Heterosynaptic Sharing of Short-Term Plasticity
journal, June 2010
- Reissner, K. J.; Pu, L.; Schaffhausen, J. H.
- Journal of Neuroscience, Vol. 30, Issue 26
Ca2+ Puffs Originate from Preestablished Stable Clusters of Inositol Trisphosphate Receptors
journal, November 2009
- Smith, I. F.; Wiltgen, S. M.; Shuai, J.
- Science Signaling, Vol. 2, Issue 98
Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to initiate Ca 2+ release
journal, April 2016
- Alzayady, Kamil J.; Wang, Liwei; Chandrasekhar, Rahul
- Science Signaling, Vol. 9, Issue 422
Fast kinetics of calcium liberation induced in Xenopus oocytes by photoreleased inositol trisphosphate
journal, January 1996
- Parker, I.; Yao, Y.; Ilyin, V.
- Biophysical Journal, Vol. 70, Issue 1
IP 3 mobilization and diffusion determine the timing window of Ca 2+ release by synaptic stimulation and a spike in rat CA1 pyramidal cells
journal, January 2009
- Manita, Satoshi; Ross, William N.
- Hippocampus
Calcium puffs are generic InsP3-activated elementary calcium signals and are downregulated by prolonged hormonal stimulation to inhibit cellular calcium responses
journal, November 2001
- Tovey, Stephen C.; de Smet, Patrick; Lipp, Peter
- Journal of Cell Science, Vol. 114, Issue 22
Localization of puff sites adjacent to the plasma membrane: Functional and spatial characterization of Ca2+ signaling in SH-SY5Y cells utilizing membrane-permeant caged IP3
journal, January 2009
- Smith, Ian F.; Wiltgen, Steven M.; Parker, Ian
- Cell Calcium, Vol. 45, Issue 1
IP3, a small molecule with a powerful message
journal, July 2013
- Decrock, Elke; De Bock, Marijke; Wang, Nan
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1833, Issue 7
Spatial trigger waves: positive feedback gets you a long way
journal, November 2014
- Gelens, Lendert; Anderson, Graham A.; Ferrell, James E.
- Molecular Biology of the Cell, Vol. 25, Issue 22
Mathematical Physiology
book, January 2009
- Keener, James; Sneyd, James
- Interdisciplinary Applied Mathematics
Works referencing / citing this record:
Astrocyte calcium signaling: Interplay between structural and dynamical patterns
journal, October 2018
- Brazhe, A. R.; Postnov, D. E.; Sosnovtseva, O.
- Chaos: An Interdisciplinary Journal of Nonlinear Science, Vol. 28, Issue 10
Regulation of bifunctional proteins in cells: Lessons from the phospholipase Cβ/G protein pathway
journal, December 2019
- Jackson, Lela; Qifti, Androniqi; Pearce, Katherine M.
- Protein Science, Vol. 29, Issue 6
Geometric principles of second messenger dynamics in dendritic spines
journal, August 2019
- Cugno, Andrea; Bartol, Thomas M.; Sejnowski, Terrence J.
- Scientific Reports, Vol. 9, Issue 1
A Model of $$\hbox {Ca}^{2+}$$ Dynamics in an Accurate Reconstruction of Parotid Acinar Cells
journal, January 2019
- Pages, Nathan; Vera-Sigüenza, Elías; Rugis, John
- Bulletin of Mathematical Biology, Vol. 81, Issue 5
Changes in Ca2+ Removal Can Mask the Effects of Geometry During IP3R Mediated Ca2+ Signals
journal, July 2019
- Piegari, Estefanía; Villarruel, Cecilia; Ponce Dawson, Silvina
- Frontiers in Physiology, Vol. 10
Geometric principles of second messenger dynamics in dendritic spines
posted_content, June 2019
- Cugno, Andrea; Bartol, Thomas M.; Sejnowski, Terrence J.
Coupling of Airway Smooth Muscle Bitter Taste Receptors to Intracellular Signaling and Relaxation Is via G αi1,2,3
journal, June 2017
- Kim, Donghwa; Woo, Jung A.; Geffken, Ezekiel
- American Journal of Respiratory Cell and Molecular Biology, Vol. 56, Issue 6
Mitochondrial Calcium Increase Induced by RyR1 and IP3R Channel Activation After Membrane Depolarization Regulates Skeletal Muscle Metabolism
journal, June 2018
- Díaz-Vegas, Alexis R.; Cordova, Alex; Valladares, Denisse
- Frontiers in Physiology, Vol. 9
Using two dyes to observe the competition of Ca 2+ trapping mechanisms and their effect on intracellular Ca 2+ signals
journal, August 2018
- Piegari, E.; Lopez, L. F.; Ponce Dawson, S.
- Physical Biology, Vol. 15, Issue 6
TRPV4 (Transient Receptor Potential Vanilloid 4) Channel–Dependent Negative Feedback Mechanism Regulates G q Protein–Coupled Receptor–Induced Vasoconstriction
journal, March 2018
- Hong, Kwangseok; Cope, Eric L.; DeLalio, Leon J.
- Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 38, Issue 3
Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling
journal, June 2017
- Shears, Stephen B.
- Journal of Cellular Physiology, Vol. 233, Issue 3
Endogenous signalling pathways and caged IP 3 evoke Ca 2+ puffs at the same abundant immobile intracellular sites
journal, September 2017
- Keebler, Michael V.; Taylor, Colin W.
- Journal of Cell Science, Vol. 130, Issue 21
Structure and Function of IP 3 Receptors
journal, February 2019
- Prole, David L.; Taylor, Colin W.
- Cold Spring Harbor Perspectives in Biology, Vol. 11, Issue 4
IP3, still on the move but now in the slow lane
journal, November 2016
- Leybaert, L.
- Science Signaling, Vol. 9, Issue 453
Geometric principles of second messenger dynamics in dendritic spines
posted_content, June 2019
- Cugno, Andrea; Bartol, Thomas M.; Sejnowski, Terrence J.
Synaptic neuron-astrocyte communication is supported by an order of magnitude analysis of inositol tris-phosphate diffusion at the nanoscale in a model of peri-synaptic astrocyte projection
journal, February 2018
- Montes de Oca Balderas, Pavel; Montes de Oca Balderas, Horacio
- BMC Biophysics, Vol. 11, Issue 1
Endogenous signalling pathways and caged IP 3 evoke Ca 2+ puffs at the same abundant immobile intracellular sites
journal, September 2017
- Keebler, Michael V.; Taylor, Colin W.
- Journal of Cell Science, Vol. 130, Issue 21
Ca2+ Microdomains in T-Lymphocytes
journal, May 2017
- Wolf, Insa M. A.; Guse, Andreas H.
- Frontiers in Oncology, Vol. 7