QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 20, Issue 1, 200-208, January 1, 2009

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-06-0555v1 20/1/200    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Du, G. Articles by Frohman, M. A. Search for Related Content PubMed PubMed Citation Articles by Du, G. Articles by Frohman, M. A.

A Lipid-signaled Myosin Phosphatase Surge Disperses Cortical Contractile Force Early in Cell Spreading

Department of Pharmacology and Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794

Submitted June 3, 2008; Revised September 10, 2008; Accepted October 9, 2008
Monitoring Editor: Robert G. Parton

When cells cease migrating through the vasculature, adhere to extracellular matrix, and begin to spread, they exhibit rapid changes in contraction and relaxation at peripheral regions newly contacting the underlying substrata. We describe here a requirement in this process for myosin II disassembly at the cell cortex via the action of myosin phosphatase (MP), which in turn is regulated by a plasma membrane signaling lipid. Cells in suspension exhibit high levels of activity of the signaling enzyme phospholipase D2 (PLD2), elevating production of the lipid second messenger phosphatidic acid (PA) at the plasma membrane, which in turn recruits MP and stores it there in a presumed inactive state. On cell attachment, down-regulation of PLD2 activity decreases PA production, leading to MP release, myosin dephosphorylation, and actomyosin disassembly. This novel model for recruitment and restraint of MP provides a means to effect a rapid cytoskeletal reorganization at the cell cortex upon demand.

* Present address: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030.

Address correspondence to: Guangwei Du (guangwei.du{at}uth.tmc.edu) or Michael A. Frohman (michael{at}pharm.stonybrook.edu).

Abbreviations used: MP, myosin phosphatase; MYPT (also called myosin-binding subunit, MBS, or M130), myosin phosphatase–targeting subunit; MLC, myosin regulatory light chain; PA, phosphatidic acid; PLD2, phospholipase D2; PP1c , protein phosphatase 1 isoform; ROCK, Rho-activated Rho kinase.

This article has been cited by other articles:

				E. Scotto-Lavino, M. Garcia-Diaz, G. Du, and M. A. Frohman Basis for the Isoform-specific Interaction of Myosin Phosphatase Subunits Protein Phosphatase 1c {beta} and Myosin Phosphatase Targeting Subunit 1 J. Biol. Chem., February 26, 2010; 285(9): 6419 - 6424. [Abstract] [Full Text] [PDF]

				W. Su, O. Yeku, S. Olepu, A. Genna, J.-S. Park, H. Ren, G. Du, M. H. Gelb, A. J. Morris, and M. A. Frohman 5-Fluoro-2-indolyl des-chlorohalopemide (FIPI), a Phospholipase D Pharmacological Inhibitor That Alters Cell Spreading and Inhibits Chemotaxis Mol. Pharmacol., March 1, 2009; 75(3): 437 - 446. [Abstract] [Full Text] [PDF]