Disease relevance of TRDN

• The average daily weight gain was 3.87 or 3.50 TDN/kg ADG [1].
• The efficacy of transdermal nitroglycerin patches, releasing 20 mg of active substance over a period of 24 h (TDN 20), was investigated in 10 patients with stable exercise-induced angina pectoris [2].

High impact information on TRDN

• This haplotype analysis excludes a number of striated muscle-expressed genes present in this region, including laminin alpha2, laminin alpha4, triadin, and phospholamban [3].
• In addition, calsequestrin activates purified RyRs lacking triadin and junctin [4].
• In mammalian striated muscles, ryanodine receptor (RyR), triadin, junctin, and calsequestrin form a quaternary complex in the lumen of sarcoplasmic reticulum [5].
• Here we tested the hypothesis that specific charged amino acids within the luminal portion of RyR mediate its direct interaction with triadin [5].
• In the present study, we have performed co-immunoprecipitation experiments and show that HRC binds directly to triadin, which is an integral membrane protein of the sarcoplasmic reticulum [6].

Biological context of TRDN

• Alanine mutagenesis within this motif demonstrated that the critical amino acids of triadin binding to calsequestrin are the even-numbered residues Lys(210), Lys(212), Glu(214), Lys(216), Gly(218), Gln(220), Lys(222), and Lys(224) [7].
• Using fluorescence in situ hybridisation, we have assigned the gene encoding human triadin to the long arm of chromosome 6 in the region 6q22-6q23 [8].
• Two insertions of 9 and 12 residues in the amino acid sequence were observed in the predicted luminal domain of triadin, although the structural and functional consequences of such insertions are expected to be minimal [8].
• These domains also exhibit sequence homology with triadin [9].
• CONCLUSIONS: We conclude that the point mutation D307H leads to a profoundly altered conformation that no longer responds normally to Ca(2+) and fails to bind normally to triadin and junctin [10].

Anatomical context of TRDN

• We demonstrated experimentally the existence of this Trisk 51 transcript in human skeletal muscle and cloned its full length cDNA [11].
• The cDNA sequence of the predicted sarcoplasmic reticulum luminal domain of human triadin diverged from that of rabbit, with an observed similarity of 82%, translating to an identity of 77% in amino acid sequence [8].
• RyRs and triadin were both detected after myotube formation and colocalized in the cytoplasm of aneural myotubes and innervated muscle fibers [12].
• The subunit-subunit contact within the ryanodine receptor complex, as well as intermolecular interactions between the ryanodine receptor and triadin, are redox sensitive, suggesting that ROS may regulate cardiac muscle Ca(2+)-signaling events [13].
• A comparison of the subcellular disposition of a range of triadin fusion peptides indicates localization either to a few large organelles as a default target or to endoplasmic reticulum when amino acids 68-98 are present and structurally intact [14].

Associations of TRDN with chemical compounds

• The lumenal domain of triadin contains multiple repeats of alternating lysine and glutamic acid residues, which have been defined as KEKE motifs and have been proposed to promote protein associations [7].
• Interaction of HRC (histidine-rich Ca(2+)-binding protein) and triadin in the lumen of sarcoplasmic reticulum [6].
• Our data suggest that HRC may play a role in the regulation of Ca(2+) release from the sarcoplasmic reticulum by interaction with triadin [6].
• The luminal but not the cytoplasmic domain of triadin-glutathione S-transferase fusion protein binds [3H]ryanodine receptor, whereas neither the cytoplasmic nor the luminal portion of triadin binds [3H]PN-200-100-labeled dihydropyridine receptor [15].
• The same three triadin peptides as well as triadin(68-267), when attached to a glutathione column, bind to the ryanodine receptor [16].

Physical interactions of TRDN

• Using surface plasmon resonance spectroscopy, we defined a discrete domain (residues 18-46) of the cytoplasmic part of triadin interacting with the purified ryanodine receptor [17].

Co-localisations of TRDN

• Triadin has been shown to co-localize with the ryanodine receptor in the sarcoplasmic reticulum membrane [17].

Regulatory relationships of TRDN

• The binding between intact triadin or expressed triadin peptides and the ryanodine receptor has been investigated using membrane overlay and affinity chromatography [16].

Other interactions of TRDN

• Although increased MOI resulted in increased expression of each receptor isoform, it did not significantly affect the immunopattern of RyRs or the expression levels of calsequestrin, triadin, or FKBP-12 [18].
• Junctin has recently been shown to bind directly to calsequestrin, the ryanodine receptor, and triadin [9].
• All of these proteins, calsequestrin, RyR, triadin, SERCAs, and sarcalumenin, are involved in calcium uptake, storage, and release [19].

Analytical, diagnostic and therapeutic context of TRDN

• Molecular cloning of the cDNA encoding human skeletal muscle triadin and its localisation to chromosome 6q22-6q23 [8].
• Expression of calsequestrin and triadin assessed by Western blotting was similar in the infant and adult groups, but junctin expression was considerably higher in the adult groups [20].
• Using in vitro binding assay and site-directed mutagenesis, we found that the second intraluminal loop of the skeletal muscle RyR1 (amino acids 4860-4917), but not the first intraluminal loop of RyR1 (amino acids 4581-4640) could bind triadin [5].
• In the present study, mouse cardiac triadin cDNAs have been identified by cDNA library screening and RT-PCR [21].
• Northern blot analysis using a cDNA probe representing the N-terminal common region of triadin revealed that the mouse triadins were present both in heart and skeletal muscles [21].

References