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

KYLE L. ELLEFSEN; IAN PARKER; SILVINA PONCE DAWSON; GEORGE D. DICKINSON; JOHN E. PEARSON

SCIENCE SIGNALING

AMER ASSOC ADVANCEMENT SCIENCE

Año: 2016 vol. 9 p. 10801 - 10810

1937-9145

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 mm2 s−1) similar to that in water, corresponding to a range of action of ~25 mm. Consequently, IP3 is generally considered a ?global? cellular messenger. We reexamined this issue by measuring local IP3-evoked Ca2+ puffs to monitor IP3 diffusing from spot photorelease in neuroblastoma cells. Fitting these data by nu- merical simulations yielded a diffusion coefficient (≤10 mm2 s−1) about 30-fold slower than that previously reported. 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 (