Regulation of Phospholipase D Activity by Actin

摘要: Many critical cellular processes, including proliferation, vesicle trafficking, and secretion, are regulated by both phospholipase D (PLD) the actin microfilament system. Stimulation of human PLD1 results in its association with detergent-insoluble cytoskeleton, but molecular mechanisms functional consequences PLD-actin interactions remain incompletely defined. Biochemical pharmacologic modulation polymerization resulted complex bidirectional effects on PLD activity, vitro vivo. Highly purified G-actin inhibited basal stimulated whereas F-actin produced opposite effects. Actin-induced activity was independent activating stimulus. The efficacy potency were isoform-specific broadly conserved among family members. Human βγ-actin only 45% as potent 40% efficacious rabbit skeletal muscle α-actin, inhibitory profile similar to single species from yeast, Saccharomyces cerevisiae. Use polymerization-specific reagents indicated that binds monomeric G-actin, well filaments. These data consistent a model which physical state cytoskeleton is determinant regulation activity.