Regulation of Phospholipase D Activity by Actin

• Published in: The Journal of biological chemistry Vol. 277; no. 52; pp. 50683 - 50692
• Main Authors: Kusner, David J., Barton, James A., Wen, Kuo-Kuang, Wang, Xuemin, Rubenstein, Peter A., Iyer, Shankar S.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 27.12.2002; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M209221200

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 βγ-actin was only 45% as potent and 40% as efficacious as rabbit skeletal muscle α-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.