Journal article
Junctophilin-2 is necessary for T-tubule maturation during mouse heart development
Cardiovascular research, Vol.100(1), pp.44-53
10/01/2013
DOI: 10.1093/cvr/cvt133
PMCID: PMC3778955
PMID: 23715556
Abstract
Transverse tubules (TTs) provide the basic subcellular structures that facilitate excitation-contraction (EC) coupling, the essential process that underlies normal cardiac contractility. Previous studies have shown that TTs develop within the first few weeks of life in mammals but the molecular determinants of this development have remained elusive. This study aims to elucidate the role of junctophilin-2 (JPH2), a junctional membrane complex protein, in the maturation of TTs in cardiomyocytes.
Using a novel cardiac-specific short-hairpin-RNA-mediated JPH2 knockdown mouse model (Mus musculus; αMHC-shJPH2), we assessed the effects of the loss of JPH2 on the maturation of the ventricular TT structure. Between embryonic day (E) 10.5 and postnatal day (P) 10, JPH2 mRNA and protein levels were reduced by >70% in αMHC-shJPH2 mice. At P8 and P10, knockdown of JPH2 significantly inhibited the maturation of TTs, while expression levels of other genes implicated in TT development remained mostly unchanged. At the same time, intracellular Ca(2+) handling was disrupted in ventricular myocytes from αMHC- shJPH2 mice, which developed heart failure by P10 marked by reduced ejection fraction, ventricular dilation, and premature death. In contrast, JPH2 transgenic mice exhibited accelerated TT maturation by P8.
Our findings suggest that JPH2 is necessary for TT maturation during postnatal cardiac development in mice. In particular, JPH2 may be critical in anchoring the invaginating sarcolemma to the sarcoplasmic reticulum, thereby enabling the maturation of the TT network.
Details
- Title: Subtitle
- Junctophilin-2 is necessary for T-tubule maturation during mouse heart development
- Creators
- Julia O Reynolds - Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, BCM 335, Houston, TX 77030, USADavid Y ChiangWei WangDavid L BeaversSayali S DixitDarlene G SkapuraAndrew P LandstromLong-Sheng SongMichael J AckermanXander H T Wehrens
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.100(1), pp.44-53
- DOI
- 10.1093/cvr/cvt133
- PMID
- 23715556
- PMCID
- PMC3778955
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Grant note
- HL090905 / NHLBI NIH HHS HD42569 / NICHD NIH HHS T32HL007676-21A1 / NHLBI NIH HHS R01 HL090905 / NHLBI NIH HHS HL091947 / NHLBI NIH HHS HL089598 / NHLBI NIH HHS HL94291 / NHLBI NIH HHS
- Language
- English
- Date published
- 10/01/2013
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094732202771
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