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Monovalent cation channel
Trimeric intracellular cation-selective channel A (TRIC-A) is a monovalent
cation
channel in the
SR and
nuclear membranes of
skeletal muscle
cells,
[5]
[6] encoded by the transmembrane protein 38A (TMEM38A)
gene. It is one of two known
TRIC proteins, the other being
TRIC-B.
Structure
TRIC-A is a 33
kDa
[7]
transmembrane protein, expressed predominantly in excitable
tissues including
skeletal muscle and
brain.
[5] Its
N-terminal region is located in the
SR
lumen
[7] or within the
nucleus while its
C-terminal region projects into the
cytoplasm.
[5] In situ, TRIC-A forms
homo-trimers, producing its "bullet-shaped"
three-dimensional structure (see
Venturi et al. (2012), Figure 1 for a three-dimensional rendering of TRIC-A).
Function
TRIC-A is permeable to both
Na+ and
K+ but not divalent cations like
Ca2+.
[5] The channel exhibits marked
voltage-dependence, becoming more open when the
cytosol is more
positively charged than the
ER
lumen. TMEM38A-
knockout
mice exhibit reduced
Ryanodine receptor 1-mediated Ca2+ release;
[5] as such, K+ flux into the
SR through TRIC-A is thought to support RyR1-mediated efflux of Ca2+ ions from the
sarcoplasmic reticulum into the
cytosol. These knockouts also develop
hypertension during early adulthood, whereas
transgenic mice
overexpressing TRIC-A develop
hypotension. These results are thought to reflect a role for TRIC-A in the
excitability of
vascular smooth muscle cells.
Clinical significance
TRIC-A has been implicated in the regulation of
arterial blood pressure through regulating the
excitability of
vascular smooth muscle cells.
[5] Several
single-nucleotide polymorphisms (SNPs) in close proximity to the TRIC-A
locus increase the risk of
hypertension and reduce the efficiency of
antihypertensive drugs in its treatment.
[8] Such SNPs are in positive
linkage disequilibrium with TRIC-A, meaning they are unlikely to be separated by
genetic recombination and so are more frequently inherited together from the same parent
chromosome. As such, TRIC-A SNPs can provide
biomarkers for the diagnosis of essential hypertension and, in future, may help to determine which treatments may be most well-suited to a given individual
[5] (see
personalized medicine).
See also
References
- ^
a
b
c
GRCh38: Ensembl release 89: ENSG00000072954 –
Ensembl, May 2017
- ^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000031791 –
Ensembl, May 2017
-
^
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
-
^
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^
a
b
c
d
e
f
g 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.
- ^
a
b Yazawa, Masayuki; Ferrante, Christopher; Feng, Jue; Mio, Kazuhiro; Ogura, Toshihiko; Zhang, Miao; Lin, Pei-Hui; Pan, Zui; Komazaki, Shinji; Kato, Kazuhiro; Nishi, Miyuki; Zhao, Xiaoli; Weisleder, Noah; Sato, Chikara; Ma, Jianjie; Takeshima, Hiroshi (5 July 2007).
"TRIC channels are essential for Ca2+ handling in intracellular stores". Nature. 448 (7149): 78–82.
Bibcode:
2007Natur.448...78Y.
doi:
10.1038/nature05928.
PMID
17611541.
S2CID
4431703.
-
^ Yamazaki, Daiju; Tabara, Yasuharu; Kita, Satomi; Hanada, Hironori; Komazaki, Shinji; Naitou, Daisuke; Mishima, Aya; Nishi, Miyuki; Yamamura, Hisao; Yamamoto, Shinichiro; Kakizawa, Sho; Miyachi, Hitoshi; Yamamoto, Shintaro; Miyata, Toshiyuki; Kawano, Yuhei; Kamide, Kei; Ogihara, Toshio; Hata, Akira; Umemura, Satoshi; Soma, Masayoshi; Takahashi, Norio; Imaizumi, Yuji; Miki, Tetsuro; Iwamoto, Takahiro; Takeshima, Hiroshi (3 August 2011).
"TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance". Cell Metabolism. 14 (2): 231–241.
doi:
10.1016/j.cmet.2011.05.011.
hdl:
2433/143634.
PMID
21803293.