SLC12A1 Membrane Protein Introduction

Introduction of SLC12A1

SLC12A1, also known as kidney-specific Na-K-Cl symporter (NKCC2), is a protein belonging to the sodium bile acid cotransporter family. It specifically exists in cells of the thick ascending limb of the loop of Henle and the macula densa in nephrons, which is the basic functional units of the kidney. Within these cells, SLC12A1 exists in the apical membrane of the nephron's lumen, which is the hollow space containing urine and therefore serves both in sodium absorption and in tubuloglomerular feedback.

Function of SLC12A1 Membrane Protein

SLC12A1 is the major transport protein by which sodium is reabsorbed from the urine. Sodium will be reabsorbed into the blood continuously and this process will contribute to the maintenance of blood pressure. Many loop diuretics can inhibit the activity of SLC12A1, which will result in impairing sodium reabsorption in the thick ascending limb of the loop of Henle. Impaired sodium reabsorption increases diuresis by three mechanisms: increasing the number of active osmolytes in urine by decreasing absorption of sodium, erasing the papillar gradient or/and inhibiting tubuloglomerular feedback Loop diuretics therefore ultimately result in decreased blood pressure. The hormone vasopressin stimulates the activity of SLC12A1. Vasopressin stimulates sodium chloride reabsorption in the thick ascending limb of the nephron by activating signaling pathways. Vasopressin can increase the traffic of SLC12A1 and phosphorylates some serine and threonine sites on the cytoplasmic N-terminal of the SLC12A1 located in the membrane, increasing its activity. Improvement of SLC12A1 activity helps water reabsorption in the collecting duct through aquaporin 2 channels by creating a hypo-osmotic filtrate.

Fig.1 Model for NaCl reabsorption in the thick ascending limb of Henle’s loop (TAL). (Jentsch, 2005)

Application of SLC12A1 Membrane Protein in Literature

1. Markadieu N. and Delpire E. Physiology and pathophysiology of SLC12A1/2 transporters. Pflugers Arch. 2014, 466(1):91-105. PubMed ID: 24097229
   
   

   The electroneutral Na⁺-K⁺-Cl^- cotransporters NKCC1 and NKCC2 belong to solute carrier family 12. They participate in the electroneutral movement of Na(+) and K(+). This article reviews the research progress of NKCC1 and NKCC2, discusses the current points of controversy, and emphasize many unanswered questions.

2. Adachi M., et al. Novel SLC12A1 (NKCC2) mutations in two families with Bartter syndrome type 1. Endocr J. 2007, 54(6):1003-7. PubMed ID: 17998760
   
   

   The article finds four novel SLC12A1 gene mutations: N117X, G257S, D792fs and N984fs in two Bartter syndrome (BS) type 1 patients.

3. Bralten L.B., et al. Integrated genomic profiling identifies candidate genes implicated in glioma-genesis and a novel LEO1-SLC12A1 fusion gene. Genes Chromosomes Cancer. 2010, 49(6):509-17. PubMed ID: 20196086
   
   

   In this article, authors identify genes involved in glioma initiation and/or progression, as well as four high-copy amplicons, which result in overexpression of the known oncogenes EGFR, MDM2, and CDK4. They only identify a homozygous deletion spanning the Pragmin gene in one sample. These results suggest that integrated genomic profiling can identify genes involved in tumor initiation, and/or progression and can be used as an approach to identify novel fusion genes.

4. Nozu K., et al. In vivo and in vitro splicing assay of SLC12A1 in an antenatal salt-losing tubulopathy patient with an intronic mutation. Hum Genet. 2009, 126(4):533-8. PubMed ID: 19513753
   
   

   In this report, authors conduct both in vivo assay of RT-PCR analysis with RNA extracted from the proband's urinary sediments and in vitro functional splicing study by minigene construction. They finally find that this intronic mutation leads to complete exon 5 skipping.

5. Alshahrani S., et al. Expression of the Slc12a1 gene in pancreatic β-cells: molecular characterization and in silico analysis. Cell Physiol Biochem. 2012, 30(1):95-112. PubMed ID: 22759959
   
   

   The findings firstly identify the NKCC2A expression in pancreatic β-cells in which it may function a role in insulin secretion.

SLC12A1 Preparation Options

Membrane protein studies have got great progress over the past few years. Based on our versatile Magic™ membrane protein production platform, we can provide a series of membrane protein preparation services in reconstitution forms as well as multiple active formats for worldwide customers. Besides, aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC12A1 antibody development services.

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

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. It’s our pleasure to boost the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Jentsch TJ, (2015). Chloride transport in the kidney: lessons from human disease and knockout mice. J Am Soc Nephrol. 16(6), 1549-61.

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