Involvement of Rho GTPases and their effectors in the secretory process of PC12 cells

Details

Serval ID
serval:BIB_5C6BE625D378
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Involvement of Rho GTPases and their effectors in the secretory process of PC12 cells
Journal
Experimental Cell Research
Author(s)
Frantz  C., Coppola  T., Regazzi  R.
ISSN
0014-4827 (Print)
Publication state
Published
Issued date
02/2002
Volume
273
Number
2
Pages
119-26
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb 15
Abstract
We investigated the involvement of Rho GTPases in the secretory process of PC12 cells. Overexpression of wild-type RhoA, Rac1, or Cdc42 did affect exocytosis. In contrast, secretion elicited by depolarizing K(+) concentrations was enhanced by the dominant negative mutants RhoA(N19), Rac1(N17), and Cdc42(N17) and was diminished by the constitutively active mutants RhoA(V14), Rac1(V12), and Cdc42(V12). The inhibition observed in the presence of RhoA(V14) was likely a result of the activation of ROK(alpha), since the catalytic domain of this kinase was able to mimic both the reorganization of the actin cytoskeleton and the decrease in exocytosis induced by the RhoA mutant. Part of the effect of Rac1(V12) may be due to POR1 activation. Thus, overexpression of full-length POR1 diminished K(+)-stimulated exocytosis, and a point mutation in the effector domain of Rac1(V12) that prevents the interaction with POR1 abolished the inhibitory effect of the GTPase. We also searched for the Cdc42(V12) target but overexpression of the Cdc42 effector WASP did not mimic the inhibition of exocytosis observed in cells transfected with the activated GTPase. Our findings indicate that different signaling cascades resulting in the activation of RhoA, Rac1, or Cdc42 can modulate the exocytotic process of neuroendocrine cells.
Keywords
Actins/metabolism *Adaptor Proteins, Signal Transducing Animals Carrier Proteins/genetics/metabolism Cytoskeleton/physiology Exocytosis/*physiology Human Growth Hormone/metabolism Humans Intracellular Signaling Peptides and Proteins Mutagenesis, Site-Directed PC12 Cells Protein-Serine-Threonine Kinases/metabolism Proteins/genetics/metabolism Rats *Signal Transduction Wiskott-Aldrich Syndrome Protein cdc42 GTP-Binding Protein/genetics/*metabolism rac1 GTP-Binding Protein/genetics/*metabolism rhoA GTP-Binding Protein/genetics/*metabolism
Pubmed
Web of science
Create date
24/01/2008 15:30
Last modification date
20/08/2019 15:14
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