JPH1 Membrane Protein Introduction

Introduction of JPH1

JPH1 is encoded by the JPH1 gene, and is also known as Junctophilin-1, JP-1 and Junctophilin type 1. JPH1 is the major JPH family member expressed in skeletal muscle but also demonstrates a low level of expression in the heart. Four junctophilin genes (JPH1-4) are known in vertebrates and encode for a family of junctional membrane complex (JMC) proteins, which are highly conserved in evolution. The JPH proteins contribute to the formation of JMCs in excitable cells by anchoring the endoplasmic reticulum (ER) to the plasma membrane (PM) or the sarcoplasmic reticulum (SR) to T-tubules in muscle cells, where these structures play a role in controlling intracellular Ca²⁺ homeostasis.

Function of JPH1 Membrane Protein

JPH1 maintains the critical ultrastructural geometry of the skeletal muscle triad which comprises three independent membranous structures including the T-tubular invagination of the sarcolemma flanked on two sides by cytosolic SR. Loss of JPH1 expression has been shown to reduce the number of intact triads and to deform intact triads. In addition to a structural role, JPH1 directly binds and regulates a number of proteins within the skeletal muscle JMC. JPH1 directly interacts with the sarcolemmal LTCC through a binding domain on JPH1 spanning from amino acids 232 to 369 within the joining region domain of the protein. What’s more, it directly interacts with sarcolemmal CAV3-encoded caveolin type 3 (Cav3). It also directly interacts with the skeletal muscle-specific, RYR1-encoded ryanodine receptor type 1 (RyR1) which mediates release of Ca²⁺ stored within the SR. This interaction is mediated through highly reactive thiol groups, which are sensitive to oxidative insult, and changes in this interaction can alter gating of RyR1.

Fig.1 The signaling pathway of JPH1 in the skeletal muscle triad (Landstrom, 2014).

Application of JPH1 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 JPH1 is the major JPH family member expressed in skeletal muscle and directly binds and regulates a number of proteins within the skeletal muscle junctional membrane complexes.

2. Pla-Martín D., et al. Junctophilin-1 is a modifier gene of GDAP1-related Charcot–Marie–Tooth disease. Hum. Mol. Genet. 2015, 24(1):213-229. PubMed ID: 25168384
   
   

   This article concludes that JPH1 and GDAP1 share a common pathway and depend on each other; therefore, JPH1 can contribute to the phenotypical consequences of GDAP1 mutations.

3. Golini L., et al. Junctophilin 1 and 2 Proteins Interact with the L-type Ca²⁺ Channel Dihydropyridine Receptors (DHPRs) in Skeletal Muscle. The Journal of Biological Chemistry. 2011, 286(51):43717-43725. PubMed ID: 22020936
   
   

   This article suggests that JPH1 and JPH2 can facilitate the assembly of DHPR with other proteins of the excitation-contraction coupling machinery and the interaction between JPs and DHPR was mediated by a region encompassing amino acids 230-369 and amino acids 216-399 in JPH1 and JPH2, respectively.

4. Murphy R.M., et al. Ca²⁺-dependent proteolysis of junctophilin-1 and junctophilin-2 in skeletal and cardiac muscle. The Journal of Physiology. 2013, 591(Pt 3):719-729. PubMed ID: 23148318
   
   

   The findings of this article show that both JPH1 and JPH2 undergo Ca²⁺-dependent proteolysis in skeletal and cardiac muscle and suggest that such proteolysis may be a significant factor in reduced Ca²⁺ release and consequent muscle weakness and cardiac dysfunction in a range of circumstances.

5. Kakizawa S., et al. Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. The EMBO Journal. 2007, 26(7):1924-1933. PubMed ID: 17347645
   
   

   This article indicates that JPH1-knockout mice with perinatal lethality, mutant skeletal muscle shows a deficiency in triad junctions and insufficient contraction due to impaired communication between dihydropyridine receptors and RyRs.

JPH1 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-JPH1 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

As a forward-looking research institute as well as a leading custom service provider in the field of membrane protein, Creative Biolabs carries multiple first-class methods that can derive high-quality service for our worldwide customers to successfully accomplish numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.

Reference

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

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.