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Regulation of phospholipase D activity by actin. Actin exerts bidirectional modulation of Mammalian phospholipase D activity in a polymerization-dependent, isoform-specific manner.

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

Pubmed ID: 12388543

Authors

  • Kusner DJ
  • Barton JA
  • Wen KK
  • Wang X
  • Rubenstein PA
  • Iyer SS

Journal

The Journal of biological chemistry

Publication Data

December 27, 2002

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01GM62302

Mesh Terms

  • Actins
  • Animals
  • Bicyclo Compounds, Heterocyclic
  • Cell Membrane
  • Cytosol
  • Deoxyribonuclease I
  • Depsipeptides
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Humans
  • Kinetics
  • Macromolecular Substances
  • Magnesium Chloride
  • Mammals
  • Marine Toxins
  • Peptides, Cyclic
  • Phalloidine
  • Phospholipase D
  • Protein Isoforms
  • Tetradecanoylphorbol Acetate
  • Thiazoles
  • Thiazolidines
  • U937 Cells