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
- Kusner DJ
- Barton JA
- Wen KK
- Wang X
- Rubenstein PA
- Iyer SS
The Journal of biological chemistry
December 27, 2002
- Agency: NIGMS NIH HHS, Id: R01GM62302
- Bicyclo Compounds, Heterocyclic
- Cell Membrane
- Deoxyribonuclease I
- Guanosine 5'-O-(3-Thiotriphosphate)
- Macromolecular Substances
- Magnesium Chloride
- Marine Toxins
- Peptides, Cyclic
- Phospholipase D
- Protein Isoforms
- Tetradecanoylphorbol Acetate
- U937 Cells
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