Interaction of Nitric Oxide Synthase with the Postsynaptic Density Protein PSD-95 and α1-Syntrophin Mediated by PDZ Domains

Brenman, Jay E.; Chao, Daniel S.; Gee, Stephen H.; McGee, Aaron W.; Craven, Sarah E.; Santillano, Daniel R; Wu, Ziqiang; Huang, Fred C.; Xia, Houhui; Peters, Matthew F.; Froehner, Stanley C.; Bredt, David S.

doi:10.1016/s0092-8674(00)81053-3

Cited by 1,523 publications

(1,232 citation statements)

References 37 publications

(28 reference statements)

Supporting

Mentioning

1,198

Contrasting

Unclassified

Order By: Relevance

“…The sequences of these clones showed that they code for truncated forms of already known proteins. The product of clone 15 is highly homologous to the PSD-95 protein (Brenman et al, 1996) and that of clone 43 to the b1-syntrophin (Ahn et al, 1994). Clone 15 encodes a protein including only the PDZ1 and PDZ2 domains, but lacking the PDZ3, SH3 and guanylate kinase domains present in the carboxy-terminal part of PSD-95.…”

Section: Binding Of Tax To Pdz Proteinsmentioning

confidence: 99%

“…It has been veri®ed for all the clones of this study that the interaction with Tax was mediated by the PDZ domain. The observation that nNOS and PSD-95 interact through their PDZ domains has shown that these motifs also exhibit protein surface interactions (Brenman et al, 1996). The internal domain of Tax involved in the interaction for clones 2, 40 and 43 could present a particular surface motif permitting association with the PDZ domain.…”

Section: Interaction Of the Viral Protein Tax With Pdz Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

et al. 1998

View full text Add to dashboard Cite

Infection by HTLV-1 has been correlated with the appearance of various proliferative or degenerative diseases. Some of these disorders have been observed in transgenic mice expressing the Tax protein, which is known to transactivate various viral and cellular promoters through interactions with several transcription factors. In this study we show that the C-terminus of this viral oncoprotein represents a motif permitting binding of Tax to the PDZ domains of several cellular proteins. A two-hybrid screen with Tax as bait indeed yielded complementary DNAs coding for six proteins including PDZ domains. Two of them correspond to truncated forms of the PSD-95 and b1-syntrophin proteins, another clone codes for a protein homologous to the product of the C. elegans gene lin-7. The other three clones code for new human members of the PDZ family of cellular proteins. The interaction of Tax with the products of these clones was con®rmed by immunoprecipitation assays in mammalian cells, and analysis of various mutants of Tax established the importance of the Cterminal amino acids for several of these interactions. These data suggest that Tax could perturb the normal function of targeted cellular proteins by strongly interacting with their PDZ domains.

show abstract

Section: Binding Of Tax To Pdz Proteinsmentioning

confidence: 99%

Section: Interaction Of the Viral Protein Tax With Pdz Proteinsmentioning

confidence: 99%

The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Skeletal muscles express two alternatively spliced nNOS isoforms, nNOSμ and nNOSβ, both of which are expressed in fast and slow muscle types (Silvagno et al 1996;Stamler and Meissner 2001;Percival et al 2010, Figure 1). nNOSμ is scaffolded to the subsarcolemmal dystrophin glycoprotein complex (DGC) and neuromuscular junction (Brenman et al 1995(Brenman et al , 1996Adams et al 2000). The sarcolemmal nNOSμ association requires α-syntrophin, dystrophin, and α-dystrobrevin (Brenman et al 1995(Brenman et al , 1996Grady et al 2000;Adams et al 2000Adams et al , 2008.…”

Section: Introductionmentioning

confidence: 99%

“…nNOSμ is scaffolded to the subsarcolemmal dystrophin glycoprotein complex (DGC) and neuromuscular junction (Brenman et al 1995(Brenman et al , 1996Adams et al 2000). The sarcolemmal nNOSμ association requires α-syntrophin, dystrophin, and α-dystrobrevin (Brenman et al 1995(Brenman et al , 1996Grady et al 2000;Adams et al 2000Adams et al , 2008. In mice, nNOSμ is not only localized at the sarcolemma, but is also normally expressed at relatively high levels in the cytoplasm (Chang et al 1996;Kameya et al 1999;Thomas et al 2003).…”

Section: Introductionmentioning

confidence: 99%

nNOS regulation of skeletal muscle fatigue and exercise performance

Percival

2011

Biophys Rev

View full text Add to dashboard Cite

Neuronal nitric oxide synthases (nNOS) are Ca 2+ /calmodulin-activated enzymes that synthesize the gaseous messenger nitric oxide (NO). nNOSμ and the recently described nNOSβ, both spliced nNOS isoforms, are important enzymatic sources of NO in skeletal muscle, a tissue long considered to be a paradigmatic system for studying NO-dependent redox signaling. nNOS is indispensable for skeletal muscle integrity and contractile performance, and deregulation of nNOSμ signaling is a common pathogenic feature of many neuromuscular diseases. Recent evidence suggests that both nNOSμ and nNOSβ regulate skeletal muscle size, strength, and fatigue resistance, making them important players in exercise performance. nNOSμ acts as an activity sensor and appears to assist skeletal muscle adaptation to new functional demands, particularly those of endurance exercise. Prolonged inactivity leads to nNOS-mediated muscle atrophy through a FoxO-dependent pathway. nNOS also plays a role in modulating exercise performance in neuromuscular disease. In the mdx mouse model of Duchenne muscular dystrophy, defective nNOS signaling is thought to restrict contractile capacity of working muscle in two ways: loss of sarcolemmal nNOSμ causes excessive ischemic damage while residual cytosolic nNOSμ contributes to hypernitrosylation of the ryanodine receptor, causing pathogenic Ca 2+ leak. This defect in Ca 2+ handling promotes muscle damage, weakness, and fatigue. This review addresses these recent advances in the understanding of nNOS-dependent redox regulation of skeletal muscle function and exercise performance under physiological and neuromuscular disease conditions.

show abstract

“…They described how the N-methyl-D-aspartate (NMDA) receptor is S-nitrosated by neuronal NOS [30] via postsynaptic density protein 95 (PSD95), which serves as a scaffold. PSD95 is known to interaction with both the neuronal NOS [31] as well as the NMDA receptor [32], supporting its role as a scaffold. However, whether disrupting PSD95 interactions alters S-nitrosation of NMDA receptor remains unclear.…”

Section: Enzymatic Regulation Of Protein S-nitrosationmentioning

confidence: 95%

How widespread is stable protein S-nitrosylation as an end-effector of protein regulation?

Wolhuter

Eaton

2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Over the last 25 years protein S-nitrosylation, also known more correctly as S-nitrosation, has been progressively implicated in virtually every nitric oxide-regulated process within the cardiovascular system. The current, widely-held paradigm is that S-nitrosylation plays an equivalent role as phosphorylation, providing a stable and controllable post-translational modification that directly regulates end-effector target proteins to elicit biological responses. However, this concept largely ignores the intrinsic instability of the nitrosothiol bond, which rapidly reacts with typically abundant thiol-containing molecules to generate more stable disulfide bonds. These protein disulfides, formed via a nitrosothiol intermediate redox state, are rationally anticipated to be the predominant endeffector modification that mediates functional alterations when cells encounter nitrosative stimuli. In this review we present evidence and explain our reasoning for arriving at this conclusion that may be controversial to some researchers in the field.

show abstract

Interaction of Nitric Oxide Synthase with the Postsynaptic Density Protein PSD-95 and α1-Syntrophin Mediated by PDZ Domains

Cited by 1,523 publications

References 37 publications

The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

nNOS regulation of skeletal muscle fatigue and exercise performance

How widespread is stable protein S-nitrosylation as an end-effector of protein regulation?

Contact Info

Product

Resources

About