JunctophilinsA Novel Family of Junctional Membrane Complex Proteins

Takeshima, Hiroshi; Komazaki, Shinji; Nishi, Miyuki; Iino, Masamitsu; Kangawa, Kenji

doi:10.1016/s1097-2765(00)00003-4

Cited by 472 publications

(777 citation statements)

References 32 publications

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“…All JPH2 mutants exhibited an altered localization pattern with respect to the SR when compared to wild type JPH2 in H9c2 cells ( Figure 3B). H9c2 cells expressing mutant JPH2 frequently displayed alteration of intracellular localization and apparent vacuolization of intracellular structures, reminiscent of the JPH2 knockout mouse ( Figure 3B) [25]. However, the SR remained intact for the majority of H9c2 cells expressing mutant JPH2 ( Figure 3C).…”

Section: Resultsmentioning

confidence: 93%

“…Since JPH2 ablation has been linked to defects in calcium handling in embryonic cardiomyocytes and adult skeletal muscle, we investigated the effects of these human JPH2 mutations on intracellular calcium signaling when expressed in HL-1 cardiomyocytes [25,27]. Here, HL-1 cells were ideally suited for this approach since they express endogenous JPH2 and display spontaneous calcium wave activity.…”

Section: Resultsmentioning

confidence: 99%

“…Such a change in the micro-architecture of the dyad would lead to ineffective signaling and result in hypertrophy. As junctophilin-2 was first discovered as a protein bridging the dyad junction, allowing proper positioning of the L-type calcium channel and ryanodine receptor to allow normal calcium signaling [25], disruption of membrane coupling may contribute to the pathogenesis observed with mutation in JPH2. This hypothesis is supported by Xu et al who recently demonstrated that the expression of JPH2 was reduced by nearly half in rats with pressure overload-induced hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

“…Junctophilins have multiple membrane occupation and recognition nexus (MORN) domains and a SR transmembrane domain thought to allow for proper localization in the dyadic cleft between the transverse tubules and SR membrane [25,26]. JPH2 knockout mice demonstrate embryonic lethality, irregular calcium handling, asynchronous and stochastic contractions, and SR segmentation, suggesting a crucial role for junctophilin-2 in facilitating intracellular calcium release and cardiac contractility [25]. In addition, disruption of JPH expression in skeletal muscle results in compromised intracellular calcium homeostasis [27].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans

Landstrom

Weisleder

Batalden

et al. 2007

Journal of Molecular and Cellular Cardiology

164

157

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans

Landstrom

Weisleder

Batalden

et al. 2007

Journal of Molecular and Cellular Cardiology

164

157

View full text Add to dashboard Cite

“…These novel repeat motifs were subsequently recognized as MORN (membrane occupation and recognition nexus) motifs. In mammalian cells, the MORN motifs are found and well studied in a protein family of junctional membrane complex proteins, exampled by JP1, and contribute to the plasma membranebinding capacity of JP-1 [27]. Whether the MORN motifs of plant PIPKs play a similar role in the regulation of subcellular localization is unknown yet, but would be a plausible hypothesis.…”

Section: Introductionmentioning

confidence: 99%

MORN motifs in plant PIPKs are involved in the regulation of subcellular localization and phospholipid binding

Lin

et al. 2006

Cell Res

101

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Multiple repeats of membrane occupation and recognition nexus (MORN) motifs were detected in plant phosphatidylinositl monophosphate kinase (PIPK), a key enzyme in PI-signaling pathway. Structural analysis indicates that all the MORN motifs (with varied numbers at ranges of 7-9), which shared high homologies to those of animal ones, were located at N-terminus and sequentially arranged, except those of OsPIPK1 and AtPIPK7, in which the last MORN motif was separated others by an ~100 amino-acid "island" region, revealing the presence of two kinds of MORN arrangements in plant PIPKs. Through employing a yeast-based SMET (sequence of membrane-targeting) system, the MORN motifs were shown being able to target the fusion proteins to cell plasma membrane, which were further confirmed by expression of fused MORN-GFP proteins. Further detailed analysis via deletion studies indicated the MORN motifs in OsPIPK1, together with the 104 amino-acid "island" region are involved in the regulation of differential subcellular localization, i.e. plasma membrane or nucleus, of the fused proteins. Fat Western blot analysis of the recombinant MORN polypeptide, expressed in Escherichia coli, showed that MORN motifs could strongly bind to PA and relatively slightly to PI4P and PI(4,5)P 2 . These results provide informative hints on mechanisms of subcellular localization, as well as regulation of substrate binding, of plant PIPKs.

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Membrane occupation and recognition nexus (MORN) motif controls protein localization and function

et al. 2022

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The membrane occupation and recognition nexus (MORN) motif was first defined in 2000, when it was identified in the junctophilin protein family. Dozens of studies have been published ever since, mainly focusing on the function of a given MORN motif-containing protein in parasites, plants or animal cells. Proteins with MORN motifs are not only expressed in most animal and plant cell types, but also significantly differ in their intracellular localization, suggesting that the MORN motifs may fulfill multiple physiological functions. Recent studies have found that MORN motif-containing proteins junctophilin-1/2 and MORN3 play a role in cardiac hypertrophy, skeletal muscle fiber stability and cancer. Hence, MORN motif-containing proteins may be exploited to develop improved treatments for various pathological conditions, such as cardiovascular diseases. Here, we review current research on MORN motif-containing proteins in different organisms and provide both ideas and approaches for follow-up exploration of their functions and applications.

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JunctophilinsA Novel Family of Junctional Membrane Complex Proteins

Cited by 472 publications

References 32 publications

Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans

Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans

MORN motifs in plant PIPKs are involved in the regulation of subcellular localization and phospholipid binding

Membrane occupation and recognition nexus (MORN) motif controls protein localization and function

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