ABCG4 Membrane Protein Introduction

Introduction of ABCG4

ABCG4, ATP-binding cassette subfamily G member 4 is a protein that in humans is encoded by the ABCG4 gene. The protein encoded by this gene is included in the ATP-binding cassette transporter (ABC protein) superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily and is expressed predominantly in liver tissue.

Function of ABCG4 Membrane Protein

ABCG4, ATP-binding cassette sub-family G member 4 belongs to the ABCG subfamily, the members of which are half transporters composed of a single trans-membrane and a single nucleotide-binding domain. It is an ATP-binding cassette trans-membrane protein which has been shown, in vitro, to participate in the cellular efflux of desmosterol and amyloid-β peptide (Aβ). ABCG4 is highly expressed in the brain and is predominantly localized to the plasma membrane, and it may function in vivo to export Aβ at the blood-brain barrier (BBB), in a process that can be antagonized by its putative natural ligand, desmosterol (and possibly cholesterol). Also, it may be involved in macrophage lipid homeostasis. Some studies indicate that ABCG4 promote cholesterol efflux from cells to high-density lipoprotein (HDL). ABCG4-induced apoptosis may implicate a new role for this protein in the clearance mechanisms within the central nervous system.

Fig.1 Computed structural and binding features of the Abcg4 dimer model. (Dodacki, 2017)

Application of ABCG4 Membrane Protein in Literature

1. Dodacki A., et al. Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide. Sci Rep. 2017, 7(1): 13393. PubMed ID: 29042617
   
   

   This article shows for the first time that ABCG4 may function in vivo to export Aβ at the blood-brain barrier (BBB), in a process that can be antagonized by its putative natural ligand, desmosterol (and possibly cholesterol).

2. Schumacher T and Benndorf RA. ABC Transport Proteins in Cardiovascular Disease-A Brief Summary. Molecules. 2017, 22(4). PubMed ID: 28383515
   
   

   This article briefly summarizes the role of ABC transporters including ABCG4 in the pharmacokinetics and disposition of drugs frequently used to treat CVD and CVD-related complications.

3. Hegyi Z and Homolya L. Functional Cooperativity between ABCG4 and ABCG1 Isoforms. PLoS One. 2016, 11(5): e0156516. PubMed ID: 27228027
   
   

   This study indicates that ABCG4 is predominantly expressed in microglial-like cells and endothelial cells in the brain, our finding of ABCG4-induced apoptosis may implicate a new role for this protein in the clearance mechanisms within the central nervous system.

4. Sano O., et al. ABCG1 and ABCG4 Suppress γ-Secretase Activity and Amyloid β Production. PLoS One. 2016, 11(5): e0155400. PubMed ID: 27196068
   
   

   This article suggests that ABCG1 and ABCG4 alter the distribution of γ-secretase on the plasma membrane, leading to the decreased γ-secretase activity and suppressed Aβ secretion. ABCG1 and ABCG4 may inhibit the development of Alzheimer's disease and can be targets for the treatment of Alzheimer's disease.

5. Dafnis I., et al. ApoE isoforms and carboxyl-terminal-truncated apoE4 forms affect neuronal BACE1 levels and Aβ production independently of their cholesterol efflux capacity. Biochem J. 2018, 475(10): 1839-1859. PubMed ID: 29743204
   
   

   This report indicates that all apoE forms affected Aβ production/oligomerization and BACE1 levels in a pattern that did not follow that of their capacity to promote ABCG1, ABCG4 or SR-BI-mediated cholesterol efflux. Overall, the data indicate that apoE-containing lipoprotein particles can have a direct effect on BACE1 levels and Aβ secretion and possibly contribute to AD pathogenetic processes, independently of their capacity to promote cholesterol efflux.

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Reference

1. Dodacki A, et al. (2017). Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide. Sci Rep. 7(1):13393.

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