FXYD5 Membrane Protein Introduction

Introduction of FXYD5

FXYD domain-containing ion transport regulator 5 (FXYD5), also known as dysadherin, is a protein that in humans is encoded by the FXYD5 gene. It belongs to the FXYD proteins family which contains seven integral membrane proteins that interact with the Na, K-ATPase and regulate its function in a tissue-specific manner. Studies have shown that FXYD5 is not only involved in the regulation of Na, K-ATPase activity but also acts as a tumorigenic protein when overexpressed. Generally, it is expressed in normal tissues, such as the alveolar epithelium. The expression of FXYD5 is elevated in metastatic tumors, which indicates that FXYD5 may act as an oncogenic marker.

Function of FXYD5 Membrane Protein

FXYD5 is a type 1 transmembrane protein that contains a putative signal sequence. It has been reported that FXYD5 is expressed in a variety of cell types, particularly abundant in intestine, spleen, lung, and kidney, and too much less extent in muscle tissues. Additional studies also recognized FXYD5 in endothelial cells and lymphocytes. As with other FXYD proteins, it specifically interacts with the Na, K-ATPase and alters its kinetics by increasing the maximal velocity. However, in addition to regulating Na, K-ATPase kinetics, FXYD5 appears to have other functions. Studies have shown that FXYD5 is unique in the FXYD family as it possesses an extended extracellular O-glycosylated domain. It has been identified as a cancer-associated protein whose expression inhibits E-cadherin and promotes metastasis. Furthermore, elevated levels of FXYD5 in tumors of patients with different types of cancer correlate with a poor prognosis, and overexpression of FXYD5 in various cell types results in the impairment of intercellular adhesion.

Fig.1 Schematic representation of signaling events leading to CCL2 accumulation in FXYD5-expressing cells. (Lubarski-Gotliv, 2016)

Application FXYD5 of Membrane Protein in Literature

1. Brazee P.L., et al. FXYD5 is an essential mediator of the inflammatory response during lung injury. Frontiers in immunology. 2017, 8:623. PubMed ID: 28620381
   
   

   This article aims to investigate the role of FXYD5 in lung inflammation and injury. It indicates that FXYD5 is a key contributor to inflammatory lung injury.

2. Lubarski-Gotliv I., et al. FXYD5 (dysadherin) may mediate metastatic progression through regulation of the β-Na+-K+-ATPase subunit in the 4T1 mouse breast cancer model. American Journal of Physiology-Cell Physiology. 2017, 313(1): C108-C117. PubMed ID: 28515087
   
   

   This article reveals that FXYD5 participates in multiple stages of metastatic development and exhibits more than one mode of E-cadherin regulation. It also suggests that differential localization of the adaptor protein Annexin A2 in FXYD5-expressing cells may correlate with matrix metalloproteinase 9 secretion and adhesion changes in 4T1 wild-type cells.

3. Tokhtaeva E., et al. FXYD5 O-glycosylated ectodomain impairs adhesion by disrupting cell-cell trans-dimerization of Na, K-ATPase β1 subunits. J Cell Sci. 2016, 129(12):2394-2406. PubMed ID: 27142834
   
   

   This article aims to investigate whether FXYD5 disrupts the trans-dimerization of Na, K-ATPase molecules located in neighboring cells. It suggests that the extracellular O-glycosylated domain of FXYD5 could impair adhesion by interfering with intercellular β1-β1 interactions, which indicates that the ratio between FXYD5 and α1-β1 heterodimer determines whether the Na, K-ATPase acts as a positive or negative regulator of intercellular adhesion.

4. Lubarski-Gotliv I., et al. FXYD5 has a pro-inflammatory role in epithelial cells. Journal of Biological Chemistry. 2016, 291(21):11072-82. PubMed ID: 27006401
   
   

   The study is conducted to further characterize the relationship between the expression of FXYD5 and CCL2 secretion. It demonstrates that transfection of an M1 epithelial cell line with FXYD5 could largely increase lipopolysaccharide (LPS) stimulated CCL2 mRNA and secretion of the translated protein.

5. Lubarski Gotliv I. FXYD5: Na+/K+-ATPase regulator in health and disease. Frontiers in cell and developmental biology. 2016, 4:26. PubMed ID: 27066483
   
   

   This article discusses the function of FXYD5 on the Na (+)/K (+)-ATPase. It suggests that FXYD5 has the ability to modulate cellular junctions, influence chemokine production, and affect cell adhesion. The accumulated data may provide a basis for understanding the molecular mechanisms underlying FXYD5 mediated phenotypes.

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Reference

1. Lubarski-Gotliv, et al. (2016). FXYD5 has a pro-inflammatory role in epithelial cells. Journal of Biological Chemistry. 291(21), 11072-82.

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