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J. Biol. Chem., Vol. 276, Issue 26, 23867-23872, June 29, 2001
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From the Physiology and Biophysics, University of Texas Medical
Branch, Galveston, Texas 77550-0641
Many animal cells release ATP into the
extracellular medium, and often this release is mechanosensitive.
However, the mechanisms underlying this release are not well
understood. Using the luciferin-luciferase bioluminescent assay we
demonstrate that a Xenopus oocyte releases ATP at a basal
rate ~0.01 fmol/s, and gentle mechanical stimulation can increase
this to 50 fmol/s. Brefeldin A, nocodazole, and
progesterone-induced- maturation block basal and mechanosensitive ATP
release. These treatments share the common feature of disrupting the
Golgi complex and vesicle trafficking to the cell surface and thereby
block protein secretion and membrane protein insertion. We propose that ATP release occurs when protein transport vesicles enriched in ATP fuse
with the plasma membrane. Collagenase, integrin-binding peptides, and
cytochalasin D also block ATP release, indicating that extracellular,
membrane and cytoskeletal elements are involved in the release process.
Elevation of intracellular Ca2+ does not evoke ATP release
but potentiates mechanosensitive ATP release. Our study
indicates a novel mechanism of mechanotransduction that would allow
cells to regulate membrane trafficking and protein transport/secretion
in response to mechanical loading.
Brefeldin A Block of Integrin-dependent
Mechanosensitive ATP Release from Xenopus Oocytes Reveals a
Novel Mechanism of Mechanotransduction*
*
This work was supported by the National Institutes of Health
and by Muscular Dystrophy Association.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Physiology and
Biophysics, University of Texas Medical Branch, 301 University Blvd.,
Galveston, TX 77550-0641. Tel.: 409-772-5464; Fax: 409-772-3381; E-mail: ohamill@utmb.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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