Stabilization of F-actin prevents cAMP-elicited Cl- secretion in T84 cells.

Shapiro, Marc J.; Matthews, Jeffrey B.; Hecht, Gail; Delp, C; Madara, James L.

doi:10.1172/jci115215

Cited by 96 publications

(70 citation statements)

References 34 publications

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“…Cytoskeletal proteins may be good candidates to interact with system A. Indeed, the concept that plasma membrane transporters may interact with cytoskeletal regulatory proteins is not new (27)(28)(29), but, to our knowledge, this is the first time that such an interaction between the cytoskeleton and an amino acid carrier has been proposed. Evidence for a direct binding between a carrier and cytoskeleton elements has been described for Na+,K+-ATPase.…”

Section: Discussionmentioning

confidence: 95%

Evidence for a regulatory protein involved in the increased activity of system A for neutral amino acid transport in osmotically stressed mammalian cells.

Ruiz-Montasell

Gómez‐Angelats

Casado

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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System A for neutral amino acid transport is Increased by hypertonic shock in NBL-1 cells previously induced to express system A activity by amino acid starvation. The hypertonicity-medated effect can be blocked by cyclobeximide but is insensitive to tuncmycin. The activity induced may be inactivated Irreversibly by the addition of system A substrates, by a rapid mehanism insensitive to cycloheximide. In CHO-Ki cells, hypertonicity increases system A activity, as has been shown in NBL-1 cells. This effect is additive to the activity produced by derepression of system A by amino acid starvation and is insensitive to tuncmycin. Furthermore, the alanine-resistant mutant CHO-K1 alar4, which bears a mutation affecting the regulatory gene RI, involved in the derepression ofsystem A activity after amino acid starvation, is still able to respond to the hypertonic shock by increasing system A activiy to a level slmllar to that described in hypertonicityinduced derepressed CHO-Ki (wild type) cells. These results suggest (i) that the hypertonicity-medated increase of system A activity occurs o h a mechanism other than that involved in system A derepresslon and (is) that a regulatory protein coded by an osmotically sensitive gene is responsible for further activation of preexisting A carriers.

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Section: Discussionmentioning

confidence: 95%

Evidence for a regulatory protein involved in the increased activity of system A for neutral amino acid transport in osmotically stressed mammalian cells.

Ruiz-Montasell

Gómez‐Angelats

Casado

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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“…None of the subunits of the V-ATPase have been shown to be phosphorylated by protein kinase A (49,50), which indicates that an indirect mechanism might be involved in the cAMPinduced apical accumulation of the pump. Interestingly, modulation of the actin cytoskeleton by cAMP has been proposed for the regulation of several membrane transporters (81)(82)(83)(84)(85)(86), and phosphorylation of RhoA by protein kinase A, leading to actin disassembly, was invoked in their regulation. In this study, depolymerization of the actin cytoskeleton by cAMP, leading to inhibition of V-ATPase endocytosis, would be compatible with the apical accumulation of V-ATPase induced by cAMP.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Actin Cytoskeleton via Gelsolin Regulates Vacuolar H+-ATPase Recycling

Beaulieu

Silva

Pastor-Soler

et al. 2005

Journal of Biological Chemistry

124

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The role of the actin cytoskeleton in regulating membrane protein trafficking is complex and depends on the cell type and protein being examined. Using the epididymis as a model system in which luminal acidification is crucial for sperm maturation and storage, we now report that modulation of the actin cytoskeleton by the calcium-activated actin-capping and -severing protein gelsolin plays a key role in regulating vacuolar

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“…Both secramine B and pirl1 prevent Cdc42-dependent actin polymerization in cell extracts and pirl1 inhibits PMA-induced actin rearrangements in monkey kidney epithelial BSC-1 cells [5,9]. Like secramine B and pirl1, NBD-phallicidin does not interfere with Ca 2+ -mediated Cl -secretion induced by carbachol [18]. Among the Rho GTPases, RhoA activation stimulates stress fiber formation and Cdc42 and Rac1 activation stimulate actinbased structures along the cell periphery [6].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Elevation of cAMP causes a loss of basement stress fibers and an increase in actin bundles along the lateral membranes of T84 cells [18]. Prevention of this actin redistribution by stabilizing the actin stress fibers with NBD-phallicidin inhibits cAMP-induced Cl -secretion in T84 cells [18]. Both secramine B and pirl1 prevent Cdc42-dependent actin polymerization in cell extracts and pirl1 inhibits PMA-induced actin rearrangements in monkey kidney epithelial BSC-1 cells [5,9].…”

Section: Discussionmentioning

confidence: 99%

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The Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cells

Pelish

Ciesla

Tanaka

et al. 2006

Biochemical Pharmacology

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Cyclic AMP-(cAMP) and calcium-dependent agonists stimulate chloride secretion through the coordinated activation of distinct apical and basolateral membrane channels and ion transporters in mucosal epithelial cells. Defects in the regulation of Cl -transport across mucosal surfaces occur with cystic fibrosis and V. cholerae infection and can be life threatening. Here we report that secramine B, a small molecule that inhibits activation of the Rho GTPase Cdc42, reduced cAMPstimulated chloride secretion in the human intestinal cell line T84. Secramine B interfered with a cAMP-gated and Ba 2+ -sensitive K + channel, presumably KCNQ1/KCNE3. This channel is required to maintain the membrane potential that sustains chloride secretion. In contrast, secramine B did not affect the Ca 2+ -mediated chloride secretion pathway, which requires a separate K + channel activity from that of cAMP. Pirl1, another small molecule structurally unrelated to secramine B that also inhibits Cdc42 activation in vitro, similarly inhibited cAMPdependent but not Ca 2+ -dependent chloride secretion. These results suggest that Rho GTPases may be involved in the regulation of the chloride secretory response and identify secramine B an inhibitor of cAMP-dependent K + conductance in intestinal epithelial cells.

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Stabilization of F-actin prevents cAMP-elicited Cl- secretion in T84 cells.

Cited by 96 publications

References 34 publications

Evidence for a regulatory protein involved in the increased activity of system A for neutral amino acid transport in osmotically stressed mammalian cells.

Evidence for a regulatory protein involved in the increased activity of system A for neutral amino acid transport in osmotically stressed mammalian cells.

Modulation of the Actin Cytoskeleton via Gelsolin Regulates Vacuolar H+-ATPase Recycling

The Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cells

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