SLC30A8 Membrane Protein Introduction

Introduction of SLC30A8

Solute carrier family 30 member 8 (SLC30A8), also known as Zinc transporter 8 (ZnT-8), is a protein that in humans is encoded by the SLC30A8 gene. The protein is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. The SLC30A8 gene is expressed at a high level only in the pancreas, especially in Langerhans islets. The protein colocalizes with insulin in the secretory pathway granules of insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to noninsulin-dependent and diabetes mellitus. Certain alleles of this gene may increase the risk of developing type 2 diabetes, but a loss-of-function mutation appears to significantly reduce the risk of diabetes.

Function of SLC30A8 Membrane Protein

Zinc plays a unique and important role in many key biological processes, such as growth, development, reproduction, and immune functions. Therefore, maintaining an adequate but tightly regulated intracellular zinc level is critical for the survival of living organisms including humans. The SLC30 family is involved in 1) transferring zinc from the cytoplasm into intracellular compartments to provide zinc for zinc-containing proteins and store zinc in the cells; 2) shuffling cytoplasmic zinc out to the extracellular space to avoid zinc toxicity.

12 rare variants in SLC30A8 have been identified through the genotyping or sequencing. SLC30A8 contains a common variant (p.Trp325Arg), which is associated with T2D risk and levels of glucose and proinsulin. Individuals carrying protein-truncating variants collectively have a 65% reduced risk of T2D. In addition, non-diabetic individuals from Iceland harboring a frameshift variant p. Lys34Serfs*50 demonstrate reduced glucose levels. Earlier functional studies of SLC30A8 indicated that reduced zinc transport may increase T2D risk. In contrast, loss-of-function mutations in humans suggest that SLC30A8 haploinsufficiency protects against T2D. Therefore, ZnT8 inhibition can be used as a therapeutic strategy in preventing T2D.

Fig.1 Solute carrier family 30 (zinc transporter), member 8.

Application of SLC30A8 Membrane Protein in Literature

1. Kleiner S., et al. Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity. Proc Natl Acad Sci U S A. 2018, 115(32):E7642-E7649. PubMed ID: 30038024
   
   

   The article reveals that the SLC30A8 R138X LOF mutation may exert beneficial effects on glucose metabolism by increasing the capacity of β-cells to secrete insulin under hyperglycemic conditions.

2. Li Y.Y., et al. Solute Carrier Family 30 Member 8 Gene 807C/T Polymorphism and Type 2 Diabetes Mellitus in the Chinese Population: A Meta-Analysis Including 6,942 Subjects. Front Endocrinol (Lausanne). 2018, 9: 263. PubMed ID: 29875737
   
   

   Authors in this group demonstrate that individuals of Chinese descent with the C allele of SLC30A8 gene 807C/T polymorphism may be more susceptible to developing T2DM.

3. Balke E.M., et al. SLC30A8 polymorphism and BMI complement HLA-A*24 as risk factors for poor graft function in islet allograft recipients. Diabetologia. 2018, 61(7): 1623-1632. PubMed ID: 29679103
   
   

   The article reports that SLC30A8 polymorphism and BMI complement HLA-A*24 and high BMI are associated with poor graft outcome.

4. Drake I., et al. A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8. Genes Nutr. 2017, 12: 30. PubMed ID: 29093761
   
   

   The article reveals that Znt5 is selectively required for the mast cell-mediated delayed-type allergic response. It is a novel participant in mast cell activation.

5. Carvalho S., et al. Differential cytolocation and functional assays of the two major human SLC30A8 (ZnT8) isoforms. J Trace Elem Med Biol. 2017, 44: 116-124. PubMed ID: 28965566
   
   

   Authors in this group study the differential cytolocation and functions of the two major human SLC30A8 (ZnT8) isoforms. It shows that differential cytolocation of ZnT8 isoforms may be associated with β-cell zinc metabolism in health and disease.

SLC30A8 Preparation Options

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