Evidence that the phosphatidylinositol cycle is linked to cell motility.
Transmembrane signaling via specific ligand/receptor interactions induces the immediate polymerization of actin and formation of microfilament assemblies close to the plasma membrane. The profilin:actin complex appears to provide the actin for this filament formation. A clue to the nature of the regulatory mechanism involved was recently found in that phosphatidylinositol 4,5-bisphosphate can bind to profilin, dissociate the profilactin complex, and thus liberate actin for polymerization. This suggests that the phosphatidylinositol (PI) cycle, which plays important roles in cellular regulation, also might control microfilament-based motility. We show here that neomycin, a drug which has a high affinity for phosphoinositides and in vivo interferes with the PI cycle, inhibits the polymerization of actin in platelets induced either by thrombin or by ADP. When ADP was used as agonist (but not in the case of thrombin) the induction of actin polymerization could also be blocked by the addition of aspirin. Introduction of Ca2+ into platelets by the use of the ionophore A23187 or stimulation of protein kinase C (PkC) by the phorbol ester TPA did not induce actin polymerization; neither did the addition of a combination of these two agents. Retinoic acid which inhibits PkC was also without effect on thrombin-induced actin polymerization.
Lassing
I
I
Department of Zoological Cell Biology, Wenner-Gren Institute, University of Stockholm, Sweden.
Lindberg
U
U
D000199:Actins / Q000097:blood; D000244:Adenosine Diphosphate / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000097:blood; D046911:Macromolecular Substances; D009355:Neomycin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000097:blood* / Q000502:physiology; D013917:Thrombin / Q000502:physiology
D000199:Actins; D008055:Lipids; D046911:Macromolecular Substances; D010716:Phosphatidylinositols; D000244:Adenosine Diphosphate; D013917:Thrombin; D009355:Neomycin; D001241:Aspirin