Scientific article
Open access

The LIM and SH3 domain-containing protein, lasp-1, may link the cAMP signaling pathway with dynamic membrane restructuring activities in ion transporting epithelia

Published inJournal of cell science, vol. 113, no. 11, p. 2035-2045
Publication date2000

Lasp-1 is a unique LIM and src homology 3 (SH3) domain-containing protein that was initially identified as a 40 kDa cAMP-dependent phosphoprotein in the HCl-secreting gastric parietal cell. Because cAMP is a potent stimulator of parietal cell acid secretion, we have hypothesized that changes in lasp-1 phosphorylation might be involved in the regulation of ion transport-related activities, perhaps by modulating interactions among cytoskeletal and/or vesicle-associated proteins. In this study, we demonstrate that the cAMP-dependent acid secretory agonist, histamine, induces a rapid, sustained rise in parietal cell lasp-1 phosphorylation and this increase in phosphorylation is closely correlated with the acid secretory response. In addition, elevation of intracellular cAMP concentrations appear to induce a partial redistribution of lasp-1 from the cell cortex, where it predominates along with the gamma-isoform of actin in unstimulated cells, to the beta-actin enriched, apically-directed intracellular canalicular region, which is the site of active proton transport in the parietal cell. Additional studies demonstrate that although lasp-1 mRNA and protein are expressed in a wide range of tissues, the expression is specific for certain actin-rich cell types present within these tissues. For example, gastric chief cells, which contain relatively little F-actin and secrete the enzyme, pepsinogen, by regulated exocytosis, do not appear to express lasp-1. Similarly, lasp-1 was not detected in pancreatic acinar cells, which secrete enzymes by similar mechanisms and also contain relatively low levels of F-actin. Lasp-1 also was not detectable in proximal tubules in the kidney, in gastrointestinal smooth muscle, heart or skeletal muscle. In contrast, expression was prominent in the cortical regions of ion-transporting duct cells in the pancreas and in the salivary parotid gland as well as in certain F-actin-rich cells in the distal tubule/collecting duct. Interestingly, moderate levels of expression were also detected in podocytes present in renal glomeruli and in vascular endothelium. In primary cultures of gastric fibroblasts, lasp-1 was present mainly within the tips of lamellipodia and at the leading edges of membrane ruffles. Taken together these results support the hypothesis that the lasp-1 plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in lasp-1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types.

  • Actins/analysis
  • Animals
  • Biological Transport/physiology
  • Blotting, Western
  • Chief Cells, Gastric/ metabolism/secretion
  • Cyclic AMP/ metabolism
  • Cytoskeleton/metabolism
  • Fluorescent Antibody Technique
  • Homeodomain Proteins/ metabolism
  • Male
  • Membrane Proteins/metabolism
  • Muscle, Skeletal/metabolism
  • Myocardium/metabolism
  • Nuclear Proteins
  • Parietal Cells, Gastric/metabolism/secretion
  • Phosphorylation
  • Protein Structure, Tertiary
  • Proteins
  • Proto-Oncogene Proteins c-myc/metabolism
  • Rabbits
  • Second Messenger Systems/physiology
  • Signal Transduction/ physiology
  • src Homology Domains/ physiology
Affiliation Not a UNIGE publication
Citation (ISO format)
CHEW, C. S. et al. The LIM and SH3 domain-containing protein, lasp-1, may link the cAMP signaling pathway with dynamic membrane restructuring activities in ion transporting epithelia. In: Journal of cell science, 2000, vol. 113, n° 11, p. 2035–2045.
Updates (1)
ISSN of the journal0021-9533

Technical informations

Creation08/27/2010 1:33:28 PM
First validation08/27/2010 1:33:28 PM
Update time03/14/2023 4:02:07 PM
Status update03/14/2023 4:02:07 PM
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