JPH3 Membrane Protein Introduction

Introduction of JPH3

JPH3 is encoded by the JPH3 gene and is also known as Junctophilin-3, JP-3, Junctophilin type 3 and Trinucleotide repeat-containing gene 22 protein. It belongs to members of the junctional membrane complex (JMC) protein family, serving to stabilize junctional membrane complexes between endoplasmic reticulum (ER) and plasma membrane (PM). JPH3 is one of the four JPH family members. JPH1-JPH4 have been identified with highly conserved across species and tissue-specific expression manner.

Function of JPH3 Membrane Protein

JPH3 is primarily expressed within the neurons of the brain. While the precise role of JPH3 remains enigmatic. An emerging body of evidence suggests that neuronal JPH3 may play roles in mediating balance and motor control through the maintenance of efficient Ca²⁺ signaling. JPH3 is essential for proper Ca²⁺-induced Ca²⁺ release during the excitation-contraction coupling. JPH3 knock-out mice demonstrate reduced balance and impaired motor coordination at 3 months of age without overt alterations in brain morphology or significant defects in molecular signaling. A follow-up study utilizing JPH3 knock-out and hemizygous knock-out mice aged to 6 and 9 months of age, identified progressive defects in neuromuscular strength, coordination, and balance which was greater in the knock-out mouse and progressive over time. In addition, JPH3 was the first member of the junctophilin family to be implicated in the pathogenesis of the human disease. A recent study of a cohort of Venezuelan subjects with HD-like syndrome found that approximately 25% (4/16) hosted JPH3 expansion mutations.

Fig.1 Diagram showing the mechanisms of JPH3 induced cell apoptosis (Hu, 2017).

Application of JPH3 Membrane Protein in Literature

1. Landstrom A.P., et al. The junctophilin family of proteins: From bench to bedside. Trends Mol. Med. 2014, 20(6):353-362. PubMed ID: 24636942
   
   

   This article reports that neuronal JPH3 may play roles in mediating balance and motor control through the maintenance of efficient Ca²⁺ signaling. In addition, JPH3 was the first member of the junctophilin family to be implicated in the pathogenesis of Huntington’s disease.

2. Krause A., et al. Junctophilin 3 (jph3) expansion mutations causing huntington disease like 2 (hdl2) are common in south african patients with african ancestry and a huntington disease phenotype. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2015, 168(7):573-585. PubMed ID: 26079385
   
   

   This article indicates that a CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2).

3. Seixas A.I., et al. (2011) Loss of junctophilin-3 contributes to huntington disease-like 2 pathogenesis. Ann. Neurol. 71(2):245-257. PubMed ID: 22367996
   
   

   The results of this article suggest that the pathogenic mechanism of HDL2 is multifactorial, involving both a toxic gain of function of JPH3 RNA and a toxic loss of JPH3 expression.

4. Hu X., et al. Epigenomic and Functional Characterization of Junctophilin 3 (JPH3) as a Novel Tumor Suppressor Being Frequently Inactivated by Promoter CpG Methylation in Digestive Cancers. Theranostics. 2017, 7(7):2150-2163. PubMed ID: 28656064
   
   

   Authors in this article identify that JPH3 is a novel TSG methylated in colorectal and gastric tumors which promotes mitochondrial-mediated apoptosis, also as a potential metastasis and survival biomarker for digestive cancers.

5. Li L., et al. Junctophilin 3 expresses in pancreatic beta cells and is required for glucose-stimulated insulin secretion. Cell Death & Disease. 2016, 7(6):e2275. PubMed ID: 27336719
   
   

   This article demonstrates that JPH3 expresses in mouse and human beta cells. si-JPH3 in mouse primary islets impairs GSIS in vitro and impairment in GSIS in si-JPH3 islets is due to changes in RyR2-[Ca²⁺] transient amplitude and ER-mitochondria contact.

JPH3 Preparation Options

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Reference

1. Hu X., et al. (2017) Epigenomic and Functional Characterization of Junctophilin 3 (JPH3) as a Novel Tumor Suppressor Being Frequently Inactivated by Promoter CpG Methylation in Digestive Cancers. Theranostics. 7(7):2150-2163.

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