The trimeric intracellular cation-selective channels or TRIC proteins are a group of homo-trimeric cation channel proteins of ~300 residues in the ER membrane. [1] There are two known TRIC proteins, TRIC-A and TRIC-B.
Channel function
TRICs are permeable to both Na+ and K+ but not divalent cations like Ca2+. [1] They exhibit marked voltage-dependence, becoming more open when the cytosol is more positively charged than the ER lumen.
TRIC-A
TRIC-A is predominantly expressed in excitable tissues including brain and skeletal muscle. [1] TRIC-A activity is thought to support RyR1-mediated efflux of Ca2+ ions from the sarcoplasmic reticulum into the cytosol.
TRIC-B
K+ flux into the ER through TRIC-B is thought to support IP3-induced efflux of Ca2+ ions through IP3-gated Ca2+ channels in the ER membrane.
Clinical significance
TRIC-A has been implicated in the regulation of arterial blood pressure through regulating the excitability of vascular smooth muscle cells. [1] Several single-nucleotide polymorphisms (SNPs) in close proximity to the TRIC-A locus and, in future, may serve as an important biomarker in the diagnosis of essential hypertension [1]
Null mutations in TMEM38B encoding TRIC-B are an uncommon but relatively severe cause of autosomal recessive osteogenesis imperfecta or "brittle bone disease". [2]
References
- ^ a b c d e Venturi, Elisa; Sitsapesan, Rebecca; Yamazaki, Daiju; Takeshima, Hiroshi (15 December 2012). "TRIC channels supporting efficient Ca2+ release from intracellular stores". European Journal of Physiology. 465 (2): 187–195. doi: 10.1007/s00424-012-1197-5. PMID 23242030. S2CID 14397400.
- ^ Cabral, Wayne A.; Ishikawa, Masaki; Garten, Matthias; Makareeva, Elena N.; Sargent, Brandi M.; Weis, MaryAnn; Barnes, Aileen M.; Webb, Emma A.; Shaw, Nicholas J.; Ala-Kokko, Leena; Lacbawan, Felicitas L.; Högler, Wolfgang; Leikin, Sergey; Blank, Paul S.; Zimmerberg, Joshua; Eyre, David R.; Yamada, Yoshihiko; Marini, Joan C. (21 July 2016). "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta". PLOS Genetics. 12 (7): e1006156. doi: 10.1371/journal.pgen.1006156. PMC 4956114. PMID 27441836.
The trimeric intracellular cation-selective channels or TRIC proteins are a group of homo-trimeric cation channel proteins of ~300 residues in the ER membrane. [1] There are two known TRIC proteins, TRIC-A and TRIC-B.
Channel function
TRICs are permeable to both Na+ and K+ but not divalent cations like Ca2+. [1] They exhibit marked voltage-dependence, becoming more open when the cytosol is more positively charged than the ER lumen.
TRIC-A
TRIC-A is predominantly expressed in excitable tissues including brain and skeletal muscle. [1] TRIC-A activity is thought to support RyR1-mediated efflux of Ca2+ ions from the sarcoplasmic reticulum into the cytosol.
TRIC-B
K+ flux into the ER through TRIC-B is thought to support IP3-induced efflux of Ca2+ ions through IP3-gated Ca2+ channels in the ER membrane.
Clinical significance
TRIC-A has been implicated in the regulation of arterial blood pressure through regulating the excitability of vascular smooth muscle cells. [1] Several single-nucleotide polymorphisms (SNPs) in close proximity to the TRIC-A locus and, in future, may serve as an important biomarker in the diagnosis of essential hypertension [1]
Null mutations in TMEM38B encoding TRIC-B are an uncommon but relatively severe cause of autosomal recessive osteogenesis imperfecta or "brittle bone disease". [2]
References
- ^ a b c d e Venturi, Elisa; Sitsapesan, Rebecca; Yamazaki, Daiju; Takeshima, Hiroshi (15 December 2012). "TRIC channels supporting efficient Ca2+ release from intracellular stores". European Journal of Physiology. 465 (2): 187–195. doi: 10.1007/s00424-012-1197-5. PMID 23242030. S2CID 14397400.
- ^ Cabral, Wayne A.; Ishikawa, Masaki; Garten, Matthias; Makareeva, Elena N.; Sargent, Brandi M.; Weis, MaryAnn; Barnes, Aileen M.; Webb, Emma A.; Shaw, Nicholas J.; Ala-Kokko, Leena; Lacbawan, Felicitas L.; Högler, Wolfgang; Leikin, Sergey; Blank, Paul S.; Zimmerberg, Joshua; Eyre, David R.; Yamada, Yoshihiko; Marini, Joan C. (21 July 2016). "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta". PLOS Genetics. 12 (7): e1006156. doi: 10.1371/journal.pgen.1006156. PMC 4956114. PMID 27441836.