Agonist-induced changes in cell shape during regulated secretion in rat pancreatic acini.
The actin cytoskeleton plays an important role in the mediation of exocytosis and the determination of cell shape. Experimentally induced changes in cell shape have been shown to affect stimulated secretion in pancreatic acini. In this study, we have examined whether physiologic agonists induce changes in acinar cell shape to modulate secretion. Computer-enhanced video microscopy, immunofluorescence confocal microscopy, and quantitative Western blotting were used to study cell shape changes and cytoskeletal dynamics in rat pancreatic acini. Amylase assays were performed to study the effect of the actin-myosin cytoskeletal antagonists latrunculin A, BDM, and ML-9 on secretion. We found that pancreatic acini underwent a prominent and reversible shape change in response to the physiologic secretory agonist cholecystokinin. This was accompanied by an apical activation of myosin II as well as a basolateral redistribution of both actin and myosin II. Cytoskeletal antagonists inhibited this shape change and attenuated stimulated amylase secretion. Therefore, in addition to acting as a barrier at the apex, the actin-myosin cytoskeleton may also function to modulate cell shape to further regulate stimulated secretion.
Torgerson
R R
RR
Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
McNiven
M A
MA
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D008297:Male; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D018715:Microscopy, Video; D018994:Myosin Light Chains / Q000037:antagonists & inhibitors / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D001381:Azepines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D019384:Nucleic Acid Synthesis Inhibitors; D013844:Thiazoles; D053778:Thiazolidines; C056218:ML 9; C004717:diacetylmonoxime; D015638:Cytochalasin D; D002766:Cholecystokinin; D000681:Amylases; D009218:Myosins; D003931:Diacetyl; C037067:latrunculin A