SIGMAR1 Membrane Protein Introduction

Introduction of SIGMAR1

The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is also known as Aging-associated gene 8 protein. It is the partner protein of the endoplasmic reticulum (ER), which regulates calcium signaling through IP3 receptor. In humans, the σ1 receptor is encoded by the SIGMAR1 gene. The mammalian σ1 receptor is a complete membrane protein with 223 amino acids. It is not homologous with other mammalian proteins, but it is significantly similar to the ERG2 gene products of yeast, which is C8-C7 sterol isomerase in the biosynthesis pathway of ergosterol. Hydropathy analysis of the σ1 receptor indicates three hydrophobic regions. Its crystal structure was published in 2016. The σ1 receptor is a transmembrane protein expressed in many different tissue types. It is particularly concentrated in certain regions of the central nervous system. It is related to several phenomena, including cardiovascular function, clinical depression, schizophrenia, the effects of cocaine abuse and cancer. The binding affinity of hundreds of synthetic compounds to the σ1 receptor is well known.

Function of SIGMAR1 Membrane Protein

The sigma-1 receptor is involved in lots of specific physiological functions ,the most important of which is to regulate Ca²⁺ release, regulate cardiac muscle cell contractility, and inhibit voltage-gated K⁺ channels. The causes of these effects are not well understood, although sigma-1 receptor is associated with a variety of signal transduction pathways. A link between sigma-1 receptor and a G-protein has been proposed, such as the resistance of one receptor, showing a high affinity binding of GTP-sensitive; however, there is some evidence against the G-protein coupling hypothesis. The sigma-1 receptor was shown to be present in a complex with voltage-gated K⁺ channels (K_v 1.4 and K_v 1.5), which led to the idea that sigma-1 receptor is a helper subunit. Sigma-1 receptor clearly binds to the IP3 receptor on the endoplasmic reticulum. Furthermore, in mature oligodendrocyte endoplasmic reticulum, sigma-1 receptor has been shown to be present in galactosylceramide. The broad range and role of ligand binding on sigma-1 receptor has led some to believe that sigma-1 receptor is an intracellular signal transduction amplifier.

Fig.1 The structure of Sigma non-opioid intracellular receptor 1.

Application of RYR3 Membrane Protein in Literature

1. Balasuriya D., et al. A Direct Interaction between the Sigma-1 Receptor and the hERG Voltage-Gated K⁺ Channel Revealed by Atomic Force Microscopy and Homogeneous Time-Resolved Fluorescence (HTRF®). The Journal of Biological Chemistry. 2014, 289 (46): 32353-32363. PubMed ID: 25266722
   
   

   This study indicated that the sigma-1 receptor may bind to hERG in the endoplasmic reticulum to help it assemble and transport to the serosa.

2. Nguyen L., et al. Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection. Advances in experimental medicine and biology. 2017, (964): 133-152. PubMed ID: 28315269
   
   

   This data supports the sigma-1 receptor as an amplifier for intracellular signaling and proposes future clinical applications of sigma-1 ligand as part of a multi-therapeutic approach to the treatment of neurodegenerative diseases.

3. Su T.P., et al. Sigma-1 Receptor as a Pluripotent Modulator in the Living System. Trends in pharmacological sciences. 2016, 37 (4): 262-278. PubMed ID: 26869505
   
   

   The authors believe that Sig-1R is a versatile modulator that produces multiple functional representations in the living system.

4. Zhu S.S., et al. Sigma-1 Receptor Antagonist BD1047 Reduces Mechanical Allodynia in a Rat Model of Bone Cancer Pain through the Inhibition of Spinal NR1 Phosphorylation and Microglia Activation. Mediators of Inflammation. 2015,: 265056. PubMed ID: 26696751
   
   

   These results indicate that sigma-1 receptor is associated with the development of bone cancer pain, and targeting sigma-1 receptor may be a new strategy for the treatment of bone cancer pain.

5. Mavlyutov T.A., et al. Role of the Sigma-1 Receptor in Amyotrophic Lateral Sclerosis (ALS). Journal of pharmacological sciences. 2015,127 (1): 10-16. PubMed ID: 25704013
   
   

   This article reveals that although the exact signal transduction pathway regulated by S1R in MN has not been elucidated, there may be direct or indirect functional interactions between S1R and voltage-gated potassium channels in ER pool and/or signaling of toadstool alkali M2 receptor in postsynaptic plasma membrane.

SIGMAR1 Preparation Options

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