The sarcolemmal calcium pump, alpha-1 syntrophin, and neuronal nitric-oxide synthase are parts of a macromolecular protein complex.
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AuthorsWilliams, Judith C.
Armesilla, Angel Luis
Mohamed, Tamer M. A.
Hagarty, Cassandra L.
McIntyre, Fiona H.
Zaki, Aly O.
Cartwright, Elizabeth J.
Buch, Mamta H.
MetadataShow full item record
AbstractThe main role of the plasma membrane Ca2+/calmodulin-dependent ATPase (PMCA) is in the removal of Ca2+ from the cytosol. Recently, we and others have suggested a new function for PMCA as a modulator of signal transduction pathways. This paper shows the physical interaction between PMCA (isoforms 1 and 4) and alpha-1 syntrophin and proposes a ternary complex of interaction between endogenous PMCA, alpha-1 syntrophin, and NOS-1 in cardiac cells. We have identified that the linker region between the pleckstrin homology 2 (PH2) and the syntrophin unique (SU) domains, corresponding to amino acids 399-447 of alpha-1 syntrophin, is crucial for interaction with PMCA1 and -4. The PH2 and the SU domains alone failed to interact with PMCA. The functionality of the interaction was demonstrated by investigating the inhibition of neuronal nitric-oxide synthase-1 (NOS-1); PMCA is a negative regulator of NOS-1-dependent NO production, and overexpression of alpha-1 syntrophin and PMCA4 resulted in strongly increased inhibition of NO production. Analysis of the expression levels of alpha-1 syntrophin protein in the heart, skeletal muscle, brain, uterus, kidney, or liver of PMCA4-/- mice, did not reveal any differences when compared with those found in the same tissues of wild-type mice. These results suggest that PMCA4 is tethered to the syntrophin complex as a regulator of NOS-1, but its absence does not cause collapse of the complex, contrary to what has been reported for other proteins within the complex, such as dystrophin. In conclusion, the present data demonstrate for the first time the localization of PMCA1b and -4b to the syntrophin.dystrophin complex in the heart and provide a specific molecular mechanism of interaction as well as functionality.
CitationThe Journal of Biological Chemistry, 281(33): 23341-23348
CollectionsMolecular Pharmacology Research Group
- In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4.
- Authors: Adams ME, Mueller HA, Froehner SC
- Issue date: 2001 Oct 1
- Vasomodulation by skeletal muscle-derived nitric oxide requires alpha-syntrophin-mediated sarcolemmal localization of neuronal Nitric oxide synthase.
- Authors: Thomas GD, Shaul PW, Yuhanna IS, Froehner SC, Adams ME
- Issue date: 2003 Mar 21
- The plasmamembrane calmodulin-dependent calcium pump: a major regulator of nitric oxide synthase I.
- Authors: Schuh K, Uldrijan S, Telkamp M, Rothlein N, Neyses L
- Issue date: 2001 Oct 15
- The alpha-syntrophin PH and PDZ domains scaffold acetylcholine receptors, utrophin, and neuronal nitric oxide synthase at the neuromuscular junction.
- Authors: Adams ME, Anderson KN, Froehner SC
- Issue date: 2010 Aug 18
- Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins.
- Authors: Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC
- Issue date: 1998 Jan 1