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Title: Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action

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 Ca 2+-liberating second messenger inositol trisphosphate (IP 3) diffuses with a coefficient (~280 μm 2 s -1) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP 3 is generally considered a “global” cellular messenger. We also reexamined this issue by measuring local IP 3-evoked Ca 2+ puffs to monitor IP 3 diffusing from spot photorelease in neuroblastoma cells. Fitting these data by numerical simulations yielded a diffusion coefficient (≤10 μm 2 s -1) about 30-fold slower than that previously reported. Here, we propose that diffusion of IP 3 in mammalian cells is hindered by binding to immobile, functionally inactive receptors that were diluted in oocyte extracts. The predicted range of action of IP 3 (<5 μm) is thus smaller than the size of typical mammalian cells, indicating that IP 3 should better be considered as a local rather than a global cellular messenger.
Authors:
 [1] ;  [1] ;  [2] ;  [3] ;  [4]
  1. Univ. of California, Irvine, CA (United States). Dept.of Neurobiology and Behavior
  2. University of Buenos Aires (UBA), Buenos Aires (Argentina). Dept. of Physics
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
  4. Univ. of California, Irvine, CA (United States). Dept.of Neurobiology and Behavior, Dept. of Physiology and Biophysics
Publication Date:
Report Number(s):
LA-UR-16-23743
Journal ID: ISSN 1945-0877; TRN: US1800210
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Science Signaling
Additional Journal Information:
Journal Volume: 9; Journal Issue: 453; Journal ID: ISSN 1945-0877
Publisher:
AAAS
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
National Institutes of Health (NIH); Fund for Scientific and Technological Research (FONCyT)
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
OSTI Identifier:
1411340