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Ecto-ATPase activity of alpha-sarcoglycan (adhalin)
1Consiglio Nazionale delle Ricerche Unit for Muscle Biology and Physiopathology, University of Padova Medical School, Viale Giuseppe Colombo 3, I-35121 Padova, Italy. betto@civ.bio.unipd.it
The Journal of Biological Chemistry
|March 13, 1999
Summary
Alpha-sarcoglycan exhibits ecto-ATPase activity, binding ATP and potentially regulating P2X receptors. Its absence in sarcoglycanopathies leads to muscle cell death via calcium overload.
Area of Science:
- Muscle biology
- Biochemistry
- Cellular physiology
Background:
- Alpha-sarcoglycan is part of the dystrophin-associated protein complex.
- Mutations in sarcoglycan genes cause muscular dystrophies (sarcoglycanopathies).
- Sarcoglycan deficiencies impact other sarcoglycans, suggesting a crucial unknown function.
Purpose of the Study:
- To investigate the functional role of alpha-sarcoglycan.
- To explore alpha-sarcoglycan's potential enzymatic activity.
- To elucidate the mechanism underlying sarcoglycanopathies.
Main Methods:
- Biochemical assays to test ATP binding and hydrolysis.
- In vitro assays using purified proteins and antibodies.
- Analysis of nucleotide-binding consensus sites.
- Detection of purinergic receptors in sarcolemmal membranes.
Main Results:
- Alpha-sarcoglycan demonstrates Mg2+-dependent ecto-ATPase activity, binding ATP.
- An antibody targeting the nucleotide-binding site inhibited this activity.
- A dystrophin-associated protein complex preparation showed Mg-ATPase activity inhibited by the antibody.
- P2X-type purinergic receptors were identified in the sarcolemmal membrane.
Conclusions:
- Alpha-sarcoglycan likely functions as an ecto-ATPase, modulating extracellular ATP levels.
- This activity may regulate P2X receptor function.
- Absence of alpha-sarcoglycan in sarcoglycanopathies leads to elevated extracellular ATP, P2X receptor overactivation, and muscle cell death due to calcium overload.