Ca²⁺ microdomains organized by junctophilins.

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Excitable cells typically possess junctional membrane complexes (JMCs) constructed by the plasma membrane and the endo/sarcoplasmic reticulum (ER/SR) for channel crosstalk. These JMCs are termed triads in skeletal muscle, dyads in cardiac muscle, peripheral couplings in smooth and developing striated muscles, and subsurface cisterns in neurons. Junctophilin subtypes contribute to the formation and maintenance of JMCs by serving as a physical bridge between the plasma membrane and ER/SR membrane in different cell types. In muscle cells, junctophilin deficiency prevents JMC formation and functional crosstalk between cell-surface Ca(2+) channels and ER/SR Ca(2+) release channels. Human genetic mutations in junctophilin subtypes are linked to congenital hypertrophic cardiomyopathy and neurodegenerative diseases. Furthermore, growing evidence suggests that dysregulation of junctophilins induces pathological alterations in skeletal and cardiac muscle.

Related collections

Most cited references 76

Record: found
Abstract: found
Article: not found

Junctophilins: a novel family of junctional membrane complex proteins.

M Iino, H Takeshima, M Nishi … (2000)

Junctional complexes between the plasma membrane (PM) and endoplasmic/sarcoplasmic reticulum (ER/ SR) are a common feature of all excitable cell types and mediate cross-talk between cell surface and intracellular ion channels. We have identified the junctophilins (JPs), a novel conserved family of proteins that are components of the junctional complexes. JPs are composed of a carboxy-terminal hydrophobic segment spanning the ER/SR membrane and a remaining cytoplasmic domain that shows specific affinity for the PM. In mouse, there are at least three JP subtypes: JP-1, -2, and -3. JP-2 is abundantly expressed in the heart, and mutant mice lacking JP-2 exhibited embryonic lethality. Cardiac myocytes from the mutant mice showed deficiency of the junctional membrane complexes and abnormal Ca2+ transients. Our results suggest that JPs are important components of junctional membrane complexes.

0 comments Cited 150 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle.

Khashayar Farsad, Harris Weisz, M Marcucci … (2002)

In striated muscle, the plasma membrane forms tubular invaginations (transverse tubules or T-tubules) that function in depolarization-contraction coupling. Caveolin-3 and amphiphysin were implicated in their biogenesis. Amphiphysin isoforms have a putative role in membrane deformation at endocytic sites. An isoform of amphiphysin 2 concentrated at T-tubules induced tubular plasma membrane invaginations when expressed in nonmuscle cells. This property required exon 10, a phosphoinositide-binding module. In developing myotubes, amphiphysin 2 and caveolin-3 segregated in tubular and vesicular portions of the T-tubule system, respectively. These findings support a role of the bilayer-deforming properties of amphiphysin at T-tubules and, more generally, a physiological role of amphiphysin in membrane deformation.

0 comments Cited 119 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

T-tubule remodeling during transition from hypertrophy to heart failure.

A Guo, Heping Cheng, Biyi Chen … (2010)

The transverse tubule (T-tubule) system is the ultrastructural substrate for excitation-contraction coupling in ventricular myocytes; T-tubule disorganization and loss are linked to decreased contractility in end stage heart failure (HF). We sought to examine (1) whether pathological T-tubule remodeling occurs early in compensated hypertrophy and, if so, how it evolves during the transition from hypertrophy to HF; and (2) the role of junctophilin-2 in T-tubule remodeling. We investigated T-tubule remodeling in relation to ventricular function during HF progression using state-of-the-art confocal imaging of T-tubules in intact hearts, using a thoracic aortic banding rat HF model. We developed a quantitative T-tubule power (TT(power)) index to represent the integrity of T-tubule structure. We found that discrete local loss and global reorganization of the T-tubule system (leftward shift of TT(power) histogram) started early in compensated hypertrophy in left ventricular (LV) myocytes, before LV dysfunction, as detected by echocardiography. With progression from compensated hypertrophy to early and late HF, T-tubule remodeling spread from the LV to the right ventricle, and TT(power) histograms of both ventricles gradually shifted leftward. The mean LV TT(power) showed a strong correlation with ejection fraction and heart weight to body weight ratio. Over the progression to HF, we observed a gradual reduction in the expression of a junctophilin protein (JP-2) implicated in the formation of T-tubule/sarcoplasmic reticulum junctions. Furthermore, we found that JP-2 knockdown by gene silencing reduced T-tubule structure integrity in cultured adult ventricular myocytes. T-tubule remodeling in response to thoracic aortic banding stress begins before echocardiographically detectable LV dysfunction and progresses over the development of overt structural heart disease. LV T-tubule remodeling is closely associated with the severity of cardiac hypertrophy and predicts LV function. Thus, T-tubule remodeling may constitute a key mechanism underlying the transition from compensated hypertrophy to HF.