CACNA2D3 Membrane Protein Introduction

Introduction of CACNA2D3

CACNA2D3 is voltage-dependent calcium channel subunit alpha-2/delta-3 that is a protein that in humans is encoded by the CACNA2D3 gene on chromosome 3. This protein encoded by CACNA2D3 gene belongs to a member of the alpha-2/delta subunit family. Furthermore, it’s a key component in the voltage-dependent calcium channel complex. As a key functional component, this calcium channel regulates the calcium influx when membrane polarization. Through interactions with alpha-1, beta, and gamma subunits, CACNA2D3 can form voltage-dependent calcium channel with a 1:1:1:1 ratio.

Function of CACNA2D3 Membrane Protein

CACNA2D3 is the alpha-2/delta subunit which is a key subunit of voltage-dependent calcium channel complex which is critically important for calcium current density and activation/inactivation kinetics of the calcium channel. CACNA2D3 is a so vital regulatory subunit for the complete functions of P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), as well as L-type (CACNA1C OR CACNA1D), while it’s not related with T-type (CACNA1G). It has been reported that methylation of this calcium channel is very important, and is associated with the metastatic phenotype of breast cancer and gastric cancer. Also, it’s essential for normal structure and function of auditory nerve synapses and is a novel candidate for auditory processing disorders. In addition, it’s related with development and progression of nasopharyngeal carcinoma.

Fig.1 The heteromultimeric voltage-sensitive Ca²⁺ channel, which comprises α1, α2δ, β and γ subunits. (Dooley, 2007)

Application ofCACNA2D3 Membrane Protein in Literature

1. Pirone A., et al. α2δ3 is essential for normal structure and function of auditory nerve synapses and is a novel candidate for auditory processing disorders. J Neurosci. 2014, 34(2): 434-45. PubMed ID: 24403143
   
   

   This article identifies a new role for α2δ3 subunit in the structure and function of specific synapses in the mammalian auditory pathway and in auditory processing disorders.

2. Wong AM., et al. Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma. Int J Cancer. 2013, 133(10): 2284-95. PubMed ID: 23649311
   
   

   This article demonstrates that α2δ3 can be regarded as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma and further research will be explored in the potential therapeutic area of CACNA2D3 associated tumor suppression in NPC.

3. Palmieri C., et al. Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas. Br J Cancer. 2012, 107(2): 375-81. PubMed ID: 22644305
   
   

   This study reveals that methylation-dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic phenotype of breast cancer and analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for the risk of development of metastatic disease.

4. Davies A., et al. The alpha2delta subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proc Natl Acad Sci U S A. 2010, 107(4): 1654-9. PubMed ID: 20080692
   
   

   This article reveals the calcium channel function and other roles in synaptogenesis of alpha2delta subunits including α2δ1, α2δ2 andα2δ3.

5. Wanajo A., et al. Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer. Gastroenterology. 2008, 135(2): 580-90. PubMed ID: 18588891
   
   

   This article shows that loss of CACNA2D3 expression through aberrant promoter hypermethylation may contribute to gastric carcinogenesis, and CACNA2D3 methylation is a useful prognostic marker for patients with advanced GC.

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Reference

1. Dooley D J, et al. (2007). Ca²⁺ channel alpha2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci. 28(2):75-82.

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