Regulation of the Actin Cytoskeleton by p125 Focal Adhesion Kinase in Rat Pancreatic Acinar Cells

Digestion ◽  
1999 ◽  
Vol 60 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Karlheinz Kiehne ◽  
Karl H. Herzig ◽  
Ulrich R. Fölsch
Keyword(s):  
Actin Cytoskeleton ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells

scholarly journals Evidence for secretion-like coupling involving pp60src in the activation and maintenance of store-mediated Ca2+ entry in mouse pancreatic acinar cells

2003 ◽  
Vol 370 (1) ◽  
pp. 255-263 ◽  
Author(s):  
Pedro C. REDONDO ◽  
Ana I. LAJAS ◽  
Ginés M. SALIDO ◽  
Antonio GONZALEZ ◽  
Juan A. ROSADO ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Acinar Cells ◽  
Coupling Model ◽  
Pancreatic Acinar Cells ◽  
Coupling Mechanism ◽  
Cell Type ◽  
Cortical Actin ◽  
Excitable Cells ◽  
Latrunculin A

Store-mediated Ca2+ entry (SMCE) is one of the main pathways for Ca2+ influx in non-excitable cells. Recent studies favour a secretion-like coupling mechanism to explain SMCE, where Ca2+ entry is mediated by an interaction of the endoplasmic reticulum (ER) with the plasma membrane (PM) and is modulated by the actin cytoskeleton. To explore this possibility further we have now investigated the role of the actin cytoskeleton in the activation and maintenance of SMCE in pancreatic acinar cells, a more specialized secretory cell type which might be an ideal cellular model to investigate further the properties of the secretion-like coupling model. In these cells, the cytoskeletal disrupters cytochalasin D and latrunculin A inhibited both the activation and maintenance of SMCE. In addition, stabilization of a cortical actin barrier by jasplakinolide prevented the activation, but not the maintenance, of SMCE, suggesting that, as for secretion, the actin cytoskeleton plays a double role in SMCE as a negative modulator of the interaction between the ER and PM, but is also required for this mechanism, since the cytoskeleton disrupters impaired Ca2+ entry. Finally, depletion of the intracellular Ca2+ stores induces cytoskeletal association and activation of pp60src, which is independent on Ca2+ entry. pp60src activation requires the integrity of the actin cytoskeleton and participates in the initial phase of the activation of SMCE in pancreatic acinar cells.

The subapical actin cytoskeleton regulates secretion and membrane retrieval in pancreatic acinar cells

1999 ◽  
Vol 112 (1) ◽  
pp. 81-96 ◽  
Author(s):  
K.M. Valentijn ◽  
F.D. Gumkowski ◽  
J.D. Jamieson
Keyword(s):  
Actin Cytoskeleton ◽  
Apical Membrane ◽  
Acinar Cells ◽  
Coupled Processes ◽  
Pancreatic Acinar Cells ◽  
Apical Plasma Membrane ◽  
Zymogen Granule ◽  
Terminal Web ◽  
Granule Membrane ◽  
Contractile Forces

We examined the effects of disruption of the actin cytoskeleton by cytochalasin D (cytoD) on basal and carbamylcholine-stimulated exocytosis and on compensatory membrane retrieval in pancreatic acinar cells. Although the involvement of actin in exocytosis is reasonably well established, its role in these coupled processes is not understood. Our findings suggested that cytoD inhibited stimulated secretion of amylase. However, morphometry revealed that exocytosis had occurred: the number of zymogen granules decreased, the size of the lumen increased, and large vacuolar structures continuous with the lumen formed into which amylase accumulated. Large amounts of amylase were released to the medium on removal of secretagogue and cytoD, suggesting that the subapical actin network provides contractile forces that expel the lumenal contents. Strikingly, we observed that at the apical pole of the cells where exocytosis occurred, cytoD induced an accumulation of membrane invaginations into a vastly enlarged apical membrane. These pits were often surrounded by a clathrin-like coat. Concomitantly, AP-2-, clathrin-, dynamin- and caveolin-like immunoreactivity concentrated around the enlarged lumina, suggesting that incorporation of zymogen granule membrane into the apical plasma membrane triggered the recruitment of these proteins. After wash out of cytoD and carbamylcholine and reformation of the subapical actin cytoskeleton, the coated invaginations largely disappeared in association with a reduction in lumenal size, and relocation of clathrin, AP-2, dynamin and caveolin into the cell. We suggest that the actin terminal web also controls compensatory membrane retrieval following exocytosis.

scholarly journals Group II p21-activated kinase, PAK4, is needed for activation of focal adhesion kinases, MAPK, GSK3, and β-catenin in rat pancreatic acinar cells

2020 ◽  
Vol 318 (3) ◽  
pp. G490-G503
Author(s):  
Irene Ramos-Álvarez ◽  
Lingaku Lee ◽  
Robert T. Jensen
Keyword(s):  
Focal Adhesion ◽  
Acinar Cell ◽  
Cellular Signaling ◽  
Acinar Cells ◽  
Signaling Cascades ◽  
Pancreatic Acinar Cells ◽  
Adapter Proteins ◽  
Group I ◽  
Group Ii

PAK4 is the only member of the Group II p21-activated kinases (PAKs) present in rat pancreatic acinar cells and is activated by gastrointestinal hormones/neurotransmitters stimulating PLC/cAMP and by various pancreatic growth factors. However, little is known of the role of PAK4 activation in cellular signaling cascades in pancreatic acinar cells. In the present study, we examined the role of PAK4’s participation in five different cholecystokinin-8 (CCK-8)-stimulated signaling pathways (PI3K/Akt, MAPK, focal adhesion kinase, GSK3, and β-catenin), which mediate many of its physiological acinar-cell effects, as well as effects in pathophysiological conditions. To define PAK4’s role, the effect of two different PAK4 inhibitors, PF-3758309 and LCH-7749944, was examined under experimental conditions that only inhibited PAK4 activation and not activation of the other pancreatic PAK, Group I PAK2. The inhibitors’ effects on activation of these five signaling cascades by both physiological and pathophysiological concentrations of CCK, as well as by 12- O-tetradecanoylphobol-13-acetate (TPA), a PKC-activator, were examined. CCK/TPA activation of focal adhesion kinases(PYK2/p125FAK) and the accompanying adapter proteins (paxillin/p130CAS), Mek1/2, and p44/42, but not c-Raf or other MAPKs (JNK/p38), were mediated by PAK4. Activation of PI3K/Akt/p70s6K was independent of PAK4, whereas GSK3 and β-catenin stimulation was PAK4-dependent. These results, coupled with recent studies showing PAK4 is important in pancreatic fluid/electrolyte/enzyme secretion and acinar cell growth, show that PAK4 plays an important role in different cellular signaling cascades, which have been shown to mediate numerous physiological and pathophysiological processes in pancreatic acinar cells. NEW & NOTEWORTHY In pancreatic acinar cells, cholecystokinin (CCK) or 12- O-tetradecanoylphobol-13-acetate (TPA) activation of focal adhesion kinases (p125FAK,PYK2) and its accompanying adapter proteins, p130CAS/paxillin; Mek1/2, p44/42, GSK3, and β-catenin are mediated by PAK4. PI3K/Akt/p70s6K, c-Raf, JNK, or p38 pathways are independent of PAK4 activation.

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