Hypotonic Activation of Volume-sensitive Outwardly Rectifying Anion Channels (VSOACs) Requires Coordinated Remodeling of Subcortical and Perinuclear Actin Filaments |
| |
Authors: | G-X?Wang Y-P?Dai S?Bongalon WJ?Hatton K?Murray JR?Hume Email author" target="_blank">IA?YambolievEmail author |
| |
Institution: | (1) Department of Pharmacology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, NV 89557-0270, USA |
| |
Abstract: | Cell volume regulation requires activation of volume-sensitive outwardly rectifying anion channels (VSOACs). The actin cytoskeleton
may participate in the activation of VSOACs but the roles of the two major actin pools remain undefined. We hypothesized that
structural reorganization of both subcortical and perinuclear actin filaments (F-actin) contributes to the hypotonic activation
of VSOACs. Hypotonic stress of pulmonary artery smooth muscle cells (PASMCs) was associated with reorganization of both peripheral
and perinuclear F-actin, and with activation of VSOACs. Preincubation with cytochalasin D caused prominent dissociation of
perinuclear, but not of subcortical F-actin. Cytochalasin D failed to induce isotonic activation and delayed the hypotonic
activation of VSOACs. F-actin stabilization by phalloidin delayed both the hypotonic stress-induced dissociation of membrane-associated
actin filaments and the activation kinetics of VSOACs. PKCε, which was proposed to phosphorylate and inhibit VSOACs, colocalized
primarily with F-actin and the net kinase activity remained unchanged during hypotonic cell swelling. In conclusion, normal
hypotonic activation of VSOACs requires disruption of peripheral F-actin but intact perinuclear F-actin; interference with
this pattern of actin reorganization delays the activation kinetics of VSOACs. The cell swelling-induced peripheral actin
dissociation may underlie the observed translocation of PKCε, which leads to a net decrease of PKCε inhibitory activity in
submembranous sites. Thus, reorganization of actin and PKCε may establish conditions for mechano- and/or signal transduction-mediated
activation of VSOACs. |
| |
Keywords: | Volume-sensitive outwardly rectifying anion channels (VSOACs) PKCε Subcortical F-actin Perinuclear F-actin PASMCs Hypotonic cell swelling |
本文献已被 PubMed SpringerLink 等数据库收录! |
|