2024-03-19T13:51:59Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00003787
2022-12-14T04:40:17Z
461:462
The proximal C-terminus of alpha(1C) subunits is necessary for junctional membrane targeting of cardiac L-type calcium channels
Nakada, Tsutomu
Flucher, Bernhard E.
Kashihara, Toshihide
Sheng, Xiaona
Shibazaki, Toshihide
Horiuchi-Hirose, Miwa
Gomi, Simmon
Hirose, Masamichi
Yamada, Mitsuhiko
This research was originally published in BIOCHEMICAL JOURNAL. Nakada T. et al., The proximal C-terminus of α1C subunits is necessary for junctional membrane targeting of cardiac L-type calcium channels. Biochem. J. 2012; 448: 221-231 (C) the Biochemical Society (2012).
cardiac myocyte
Ca-v 1.2
couplon
excitation-contraction coupling
junctional membrane complex
In cardiac myocytes, LTCCs (L-type calcium channels) form a functional signalling complex with ryanodine receptors at the JM (junctional membrane). Although the specific localization of LTCCs to the JM is critical for excitation-contraction coupling. their targeting mechanism is unclear. Transient transfection of GFP (green fluorescent protein)-alpha(1S) or GFP-alpha(1C) but not P/Q-type calcium channel alpha(1A), in dysgenic (alpha(1S)-null) GLT myotubes results in correct targeting of these LTCCs to the JMs and restoration of action-potential-induced Ca2+ transients. To identify the sequences of alpha(1C) responsible for JM targeting, we generated a range of alpha(1C)-alpha(1A) chimaeras, deletion mutants and alanine substitution mutants and studied their targeting properties in GLT myotubes. The results revealed that amino acids L-1681 QAGLRTL(1688) and P(1693)EIRRAIS(1700), predicted to form two adjacent alpha-helices in the proximal C-terminus, are necessary for the JM targeting of alpha(1C). The efficiency of restoration of action-potential-induced Ca2+ transients in GLT myotubes was significantly decreased by mutations in the targeting motif. JM targeting was not disrupted by the distal C-terminus of alpha(1C) which binds to the second alpha-helix. Therefore we have identified a new structural motif in the C-terminus of alpha(1C) that mediates the targeting of cardiac LTCCs to JMs independently of the interaction between proximal and distal C-termini of alpha(1C).
Article
BIOCHEMICAL JOURNAL. 448:221-231 (2012)
PORTLAND PRESS LTD
2012-12
eng
journal article
AM
http://hdl.handle.net/10091/16907
https://soar-ir.repo.nii.ac.jp/records/3787
https://pubmed.ncbi.nlm.nih.gov/22928916
22928916
https://doi.org/10.1042/BJ20120773
10.1042/BJ20120773
0264-6021
AA10649144
BIOCHEMICAL JOURNAL
448
221
231
https://soar-ir.repo.nii.ac.jp/record/3787/files/Proximal_C-terminus_α1C_subunits_necessary_junctional_membrane-targeting.pdf
application/pdf
1.6 MB
2015-09-24