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Myosin phosphatase targeting subunit 1 affects cell migration by regulating myosin phosphorylation and actin assembly.
- Source :
-
Experimental cell research [Exp Cell Res] 2005 Apr 01; Vol. 304 (2), pp. 506-17. Date of Electronic Publication: 2004 Dec 30. - Publication Year :
- 2005
-
Abstract
- Myosin II plays important roles in many contractile-like cell functions, including cell migration, adhesion, and retraction. Myosin II is activated by regulatory light chain (RLC) phosphorylation whereas RLC dephosphorylation by myosin light chain phosphatase containing a myosin phosphatase targeting subunit (MYPT1) leads to myosin inactivation. HeLa cells contain MYPT1 in addition to a newly identified human variant 2 containing an internal deletion. RLC dephosphorylation, cell migration, and adhesion were inhibited when either or both MYPT1 isoforms were knocked down by RNA interference. RLC was highly phosphorylated (60%) when both isoforms were suppressed by siRNA treatment relative to control cells (10%) with serum-starvation and ROCK inhibition. Prominent stress fibers and focal adhesions were associated with the enhanced RLC phosphorylation. The reintroduction of MYPT1 or variant 2 in siRNA-treated cells decreased stress fibers and focal adhesions. MYPT1 knockdown also led to an increase of F-actin relative to G-actin in HeLa cells. The myosin inhibitor blebbistatin did not inhibit this effect, indicating MYPT1 likely affects actin assembly independent of RLC phosphorylation. Proper expression of MYPT1 or variant 2 is critical for RLC phosphorylation and actin assembly, thus maintaining normal cellular functions by simultaneously controlling cytoskeletal architecture and actomyosin activation.
- Subjects :
- Culture Media, Serum-Free pharmacology
Down-Regulation physiology
Focal Adhesions metabolism
HeLa Cells
Heterocyclic Compounds, 4 or More Rings pharmacology
Humans
Intracellular Signaling Peptides and Proteins
Myosin-Light-Chain Phosphatase genetics
Myosin-Light-Chain Phosphatase metabolism
Myosins antagonists & inhibitors
Phosphorylation
Protein Isoforms genetics
Protein Isoforms metabolism
Protein Serine-Threonine Kinases antagonists & inhibitors
Protein Serine-Threonine Kinases metabolism
RNA Interference
Stress Fibers metabolism
rho-Associated Kinases
Actins metabolism
Cell Movement physiology
Myosin Light Chains metabolism
Myosin Type II metabolism
Myosin-Light-Chain Phosphatase physiology
Myosins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0014-4827
- Volume :
- 304
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 15748895
- Full Text :
- https://doi.org/10.1016/j.yexcr.2004.11.025