FZD1 Membrane Protein Introduction

Introduction of FZD1

FZD1, also known as frizzled class receptor 1, frizzled family receptor 1, frizzled (Drosophila) homolog 1, Fz-1, hFz1 or FzE1, is a transmembrane protein that consists of 647 amino acids and has a molecular mass of about 71 kDa. In humans, it is encoded by the FZD1 gene located on the chromosome 7q21.13. The FZD1 protein contains a signal peptide, seven transmembrane domains, a cysteine-rich domain (CRD) in the N-terminal extracellular region, and a C-terminal PDZ domain-binding motif. It is a member of the G-protein coupled receptor Fz/Smo family and employed as a receptor in the Wnt pathway and other signaling pathways. FZD1 is expressed on the heart, lung, kidney, pancreas, prostate, ovary, placenta in adults, as well as in the fetal lung and kidney. Northern blot analysis displays that its transcript is a 4.5-kb mRNA found in varieties of tissues.

Function of FZD1 Membrane Protein

FZD1 functions as a receptor for Wnt proteins, secreted cell signaling proteins that involved in development and homeostasis. And it binds Wnt signaling proteins relying on its extracellular CRD structure. Most of the frizzled receptors are coupled to the canonical β-catenin signaling pathway, which brings out an activation of disheveled proteins, suppression of GSK-3 kinase, nuclear accumulation of β-catenin, along with activation of Wnt target genes. Frizzled proteins and such genes coding for them have been identified in a number of animals, ranging from sponges to humans. And these type proteins play critical roles in governing cell polarity, embryonic development, neural synapses formation, cell proliferation, and lots of other processes in developing and adult individuals. Additionally, there is an important paralog of FZD1 gene is FZD7 and they share 74% protein sequence identity with each other.

Fig.1 Model of Wnt5a/Fzd5 and Wnt3a/Fzd1 as modulators of the inflammatory response of macrophages to microbial stimuli. (Schaale, 2011)

Application of FZD1 Membrane Protein in Literature

1. Wang Y.H., et al. Knockdown of the Wnt receptor Frizzled-1 (FZD1) reduces MDR1/P-glycoprotein expression in multidrug resistant leukemic cells and inhibits leukemic cell proliferation. Leuk Res. 2018, 67: 99-108. PubMed ID: 29482174
   
   

   The FZD1 receptor of Wnt is implicated in multidrug resistance (MDR) in several solid tumors, but it rarely reported in acute myeloid leukemia (AML). Authors concluded after assays that the activated FZD1 detected in leukemic cells may be confer acquired drug resistance, while FZD1 silencing is likely more effective in reversing MDR.

2. Han S., et al. Substratum stiffness tunes proliferation downstream of Wnt3a in part by regulating integrin-linked kinase and frizzled-1. J Cell Sci. 2018,131(8). PubMed ID: 29588395
   
   

   This review showed that integrin-linked kinase (ILK) can regulate the expression of frizzled-1 (Fzd1), a Wnt receptor, implying that the presence of a positive feedback between ILK, Fzd1, and Wnt3a. The results may indicate that tissue mechanics modulates the cellular response to Wnt signaling under physiological and pathological microenvironmental circumstances.

3. Fan J., et al.Recombinant frizzled1 protein attenuated cardiac hypertrophy after myocardial infarction via the canonical Wnt signaling pathway. Oncotarget. 2017, 9(3): 3069-3080. PubMed ID: 29423029
   
   

   Activation of classical Wnt signaling induced by myocardial infarction (MI), is inhibited in the left ventricles of the MI-mice treated by recombinant FZD1 protein (RFP). Authors concluded that the immunization of RFP can attenuate cardiac hypertrophy and improved cardiac function in the MI mice by blocking the Wnt pathway.

4. Yang L., et al. Overexpression of FZD1 and CAIX are Associated with Invasion, Metastasis, and Poor-Prognosis of the Pancreatic Ductal Adenocarcinoma. PatholOncol Res. 2017. PubMed ID: 28921449
   
   

   About 80% of patient cases with pancreatic ductal adenocarcinoma (PDAC) have metastatic symptoms with poor prognosis. This article showed that positively expressed FZD1 and CAIX are poor prognostic factors in patients with PDAC. These two may be significant biological markers for PDAC carcinogenesis, invasion, metastasis, and prognosis.

5. Su W., et al. MiR-135b reverses chemoresistance of non-small cell lung cancer cells by down regulation of FZD1. Biomed Pharmacother. 2016, 84: 123-129. PubMed ID: 27643554
   
   

   The chemoresistance of non-small cell lung cancer (NSCLC) frequently limits the clinical efficacy of therapeutic methods. And few studies have reported the regulation of miR-135b and Frizzled-1 (FZD1) in NSCLC chemoresistance. This review indicated that miR-135b amplifications suppress NSCLC chemoresistance through directly mediating FZD1 downregulations.

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Reference

1. Schaale K, et al. (2011). Wnt signaling in macrophages: augmenting and inhibiting mycobacteria-induced inflammatory responses. Eur J Cell Biol. 90(6-7), 553-9.

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