Inositol (1,4,5)-trisphosphate receptor links to filamentous actin are important for generating local Ca2+ signals in pancreatic acinar cells

J Cell Sci. 2005 Mar 1;118(Pt 5):971-80. doi: 10.1242/jcs.01693. Epub 2005 Feb 15.


We explored a potential structural and functional link between filamentous actin (F-actin) and inositol (1,4,5)-trisphosphate receptors (IP(3)Rs) in mouse pancreatic acinar cells. Using immunocytochemistry, F-actin and type 2 and 3 IP(3)Rs (IP(3)R2 and IP(3)R3) were identified in a cellular compartment immediately beneath the apical plasma membrane. In an effort to demonstrate that IP(3)R distribution is dependent on an intact F-actin network in the apical subplasmalemmal region, cells were treated with the actin-depolymerising agent latrunculin B. Immunocytochemistry indicated that latrunculin B treatment reduced F-actin in the basolateral subplasmalemmal compartment, and reduced and fractured F-actin in the apical subplasmalemmal compartment. This latrunculin-B-induced loss of F-actin in the apical region coincided with a reduction in IP(3)R2 and IP(3)R3, with the remaining IP(3)Rs localized with the remaining F-actin. Experiments using western blot analysis showed that IP(3)R3s are resistant to extraction by detergents, which indicates a potential interaction with the cytoskeleton. Latrunculin B treatment in whole-cell patch-clamped cells inhibited Ca(2+)-dependent Cl(-) current spikes evoked by inositol (2,4,5)-trisphosphate; this is due to an inhibition of the underlying local Ca(2+) signal. Based on these findings, we suggest that IP(3)Rs form links with F-actin in the apical domain and that these links are essential for the generation of local Ca(2+) spikes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry*
  • Actin Cytoskeleton / metabolism
  • Actins / chemistry
  • Actins / metabolism
  • Animals
  • Blotting, Western
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Channels / physiology*
  • Calcium Signaling
  • Cell Membrane / metabolism
  • Cytoskeleton / metabolism
  • Detergents / pharmacology
  • Electrophysiology
  • Gelsolin / chemistry
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry
  • Inositol 1,4,5-Trisphosphate Receptors
  • Inositol Phosphates / metabolism
  • Male
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Pancreas / cytology*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology
  • Thiazolidines


  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Calcium Channels
  • Detergents
  • Gelsolin
  • Inositol 1,4,5-Trisphosphate Receptors
  • Inositol Phosphates
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidines
  • Green Fluorescent Proteins
  • inositol 2,4,5-trisphosphate
  • latrunculin B
  • Calcium