Role of actin filament organization in cell volume and ion channel regulation.
The actin cytoskeleton is an intracellular structure, which is involved in the onset and control of cell shape and function. In order for this relevant network to control its own and thus cell volume, specific interactions between the actin cytoskeleton and ion channel regulation controlling intracellular salt and water homeostasis may be invoked. The hypotonic shock-induced, cell volume regulatory decrease (RVD) of most eukaryotic cells is a particularly useful example, as it is initiated and regulated by concerted processes involving both adaptive changes in actin filament organization and bulk fluid extrusion triggered by saline movement and the consequent decrease in cell water. The onset of RVD is linked to the selective activation of osmotically-sensitive ion channels and other relevant ion transport mechanisms involved in the net ionic movement from the cytosol. Such regulatory processes, entailing effector changes in actin filament organization which target the plasma membrane, are largely unknown. In this report, recent studies are summarized implicating dynamic changes in gel properties of the actin cytoskeleton as the effector mechanism in the regulation of ion channel activity, and thus cell volume, in human melanoma cells. Based on the characterization of the hypotonic cell volume regulatory response of human melanoma cells devoid of a functional actin-binding protein (ABP-280, a filamin homolog) and their genetically rescued counterpart transfected with a functional ABP, a hypothesis is raised which is consistent with a regulatory "sensory" mechanism based on the ability of actin networks to respond to changes in the intracellular water-salt homeostasis, which in turn effects signals controlling membrane function, including ion channel activity.
Cantiello
H F
HF
Renal Unit, Massachusetts General Hospital East, Charlestown 02129, USA.
D000199:Actins / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D007038:Hypotonic Solutions; D007473:Ion Channels / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism; D014882:Water-Electrolyte Balance
D000199:Actins; D007038:Hypotonic Solutions; D007473:Ion Channels