The molecular basis of leukocyte adhesion involving phosphatidic acid and phospholipase D.

Autor:	Speranza F; From the Department of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio 45435., Mahankali M; From the Department of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio 45435., Henkels KM; From the Department of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio 45435., Gomez-Cambronero J; From the Department of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio 45435 julian.cambronero@wright.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2014 Oct 17; Vol. 289 (42), pp. 28885-97. Date of Electronic Publication: 2014 Sep 02.
DOI:	10.1074/jbc.M114.597146
Abstrakt:	Defining how leukocytes adhere to solid surfaces, such as capillary beds, and the subsequent migration through the extracellular matrix, is a central biological issue. We show here that phospholipase D (PLD) and its enzymatic reaction product, phosphatidic acid (PA), regulate cell adhesion of immune cells (macrophages and neutrophils) to collagen and have defined the underlying molecular mechanism in a spatio-temporal manner that coincides with PLD activity timing. A rapid (t½ = 4 min) and transient activation of the PLD1 isoform occurs upon adhesion, and a slower (t½ = 7.5 min) but prolonged (>30 min) activation occurs for PLD2. Importantly, PA directly binds to actin-related protein 3 (Arp3) at EC50 = 22 nm, whereas control phosphatidylcholine did not bind. PA-activated Arp3 hastens actin nucleation with a kinetics of t½ = 3 min at 300 nm (compared with controls of no PA, t½ = 5 min). Thus, PLD and PA are intrinsic components of cell adhesion, which reinforce each other in a positive feedback loop and react from cues from their respective solid substrates. In nascent adhesion, PLD1 is key, whereas a sustained adhesion in mature or established focal points is dependent upon PLD2, PA, and Arp3. A prolonged adhesion could effectively counteract the reversible intrinsic nature of this cellular process and constitute a key player in chronic inflammation. (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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