Mutation of junctophilin type 2 associated with hypertrophic cardiomyopathy

Matsushita, Yoshihisa; Furukawa, Toru; Kasanuki, Hiroshi; Nishibatake, Makoto; Kurihara, Yachiyo; Ikeda, Atsushi; Kamatani, Naoyuki; Takeshima, Hiroshi; Matsuoka, Rumiko

doi:10.1007/s10038-007-0149-y

Cited by 79 publications

(72 citation statements)

References 30 publications

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“…Recently, several missense mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM) in patients in the US (27) and Japan (31). Conservation of the residues affected by these disease-associated mutations (S101R, Y141H, S165F, and G505S) is shown in Fig.…”

Section: Human Disease-associated Mutations In Jph2mentioning

confidence: 99%

Molecular evolution of the junctophilin gene family

Garbino

Oort

Dixit

et al. 2009

Physiological Genomics

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Junctophilins (JPHs) are members of a junctional membrane complex protein family important for the physical approximation of plasmalemmal and sarcoplasmic/endoplasmic reticulum membranes. As such, JPHs facilitate signal transduction in excitable cells between plasmalemmal voltagegated calcium channels and intracellular calcium release channels. To determine the molecular evolution of the JPH gene family, we performed a phylogenetic analysis of over 60 JPH genes from over 40 species and compared conservation across species and different isoforms. We found that JPHs are evolutionary highly conserved, in particular the membrane occupation and recognition nexus motifs found in all species. Our data suggest that an ancestral form of JPH arose at the latest in a common metazoan ancestor and that in vertebrates four isoforms arose, probably following two rounds of whole genome duplications. By combining multiple prediction techniques with sequence alignments, we also postulate the presence of new important functional regions and candidate sites for posttranslational modifications. The increasing number of available sequences yields significant insight into the molecular evolution of JPHs. Our analysis is consistent with the emerging concept that JPHs serve dual important functions in excitable cells: structural assembly of junctional membrane complexes and regulation of intracellular calcium signaling pathways.

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Section: Human Disease-associated Mutations In Jph2mentioning

confidence: 99%

Molecular evolution of the junctophilin gene family

Garbino

Oort

Dixit

et al. 2009

Physiological Genomics

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“…Recent studies have identified mutations in the human JP-2 gene that lead to hypertrophic cardiomyopathy (HCM) and consequences in cellular Ca 2+ handling [40]. Other JP-2 mutations in a separate cohort suggest that polymorphisms in the JP-2 gene that link to HCM may be common in various populations [41]. Additional studies have also established that JP-2 levels are down-regulated in mouse models of hypertrophic and dilated cardiomyopathies [42].…”

Section: Junctophilins Span the Cytoplasmic Space In Junctions To Linmentioning

confidence: 99%

“…[40] in black; Ref. [41] in blue). Numerous studies have identified triplet repeats in JP-3 exon 2a that result in Huntington's disease-like symptoms.…”

Section: Importance Of Tric In Physiology and Pathophysiologymentioning

confidence: 99%

Immuno-proteomic approach to excitation–contraction coupling in skeletal and cardiac muscle: Molecular insights revealed by the mitsugumins

Weisleder

Takeshima

2008

Cell Calcium

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A comprehensive understanding of excitation-contraction (E-C) coupling in skeletal and cardiac muscle requires that all the major components of the Ca 2+ release machinery be resolved. We utilized a unique immuno-proteomic approach to generate a monoclonal antibody library that targets proteins localized to the skeletal muscle triad junction, which provides a structural context to allow efficient E-C coupling. Screening of this library has identified several mitsugumins (MG); proteins that can be localized to the triad junction in mammalian skeletal muscle. Many of these proteins, including MG29 and junctophilin, are important components in maintaining the structural integrity of the triad junction. Other triad proteins, such as calumin, play a more direct role in regulation of muscle Ca 2+ homeostasis. We have recently identified a family of trimeric intracellular cation-selective (TRIC) channels that allow for K + movement into the endoplasmic or sarcoplasmic reticulum to counter a portion of the transient negative charge produced by Ca 2+ release into the cytosol. Further study of TRIC channel function and other novel mitsugumins will increase our understanding of E-C coupling and Ca 2+ homoeostasis in muscle physiology and pathophysiology.

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“…Mutations in JP2 have been linked to hypertrophic cardiomyopathy and Ca 2+ handling dysfunction (Landstrom et al, 2007;Matsushita et al, 2007). Altered expression of JP2 is observed in models of cardiomyopathy (Minamisawa et al, 2004), and as an early event in the transition towards heart failure (Xu et al, 2007).…”

Section: Disruption Of Membrane Cross-talk Following Agingmentioning

confidence: 99%

Altered Ca2+ sparks in aging skeletal and cardiac muscle

Weisleder

2008

Ageing Research Reviews

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Ca 2+ sparks are the fundamental units that comprise Ca 2+ -induced Ca 2+ release (CICR) in striated muscle cells. In cardiac muscle, spontaneous Ca 2+ sparks underlie the rhythmic CICR activity during heart contraction. In skeletal muscle, Ca 2+ sparks remain quiescent during the resting state and are activated in a plastic fashion to accommodate various levels of stress. With aging, the plastic Ca 2+ spark signal becomes static in skeletal muscle, whereas loss of CICR control leads to leaky Ca 2+ spark activity in aged cardiomyocytes. Ca 2+ spark responses reflect the integrated function of the intracellular Ca 2+ regulatory machinery centered around the triad or dyad junctional complexes of striated muscles, which harbor the principal molecular players of excitation-contraction coupling. This review highlights the contribution of age-related modification of the Ca 2+ release machinery and the effect of membrane structure and membrane cross-talk on the altered Ca 2+ spark signaling during aging of striated muscles.

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Mutation of junctophilin type 2 associated with hypertrophic cardiomyopathy

Cited by 79 publications

References 30 publications

Molecular evolution of the junctophilin gene family

Molecular evolution of the junctophilin gene family

Immuno-proteomic approach to excitation–contraction coupling in skeletal and cardiac muscle: Molecular insights revealed by the mitsugumins

Altered Ca2+ sparks in aging skeletal and cardiac muscle

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