Frzb (pronounced like the toy ''frisbee'') is a Wnt-binding

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

especially important in

embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

. It is a competitor for the cell-surface G-protein receptor

Frizzled Frizzled is a family of atypical G protein-coupled receptors that serve as receptors in the Wnt signaling pathway and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled in the cytosol. Species distribution Fr ...

. Frizzled is a tissue polarity gene in ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

'' and encodes integral proteins that function as cell-surface receptors for Wnts called serpentine receptors. The integral membrane proteins contain a

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, some ...

-rich domain thought to be the Wnt binding domain in extracellular region. The signals are initiated at the 7 transmembrane domain and transmitted through receptor coupling to G-proteins. This protein is expressed in

chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and prote ...

s making it important in skeletal development in the embryo and fetus. Frzb is localized in the extracellular plasma membrane. Unlike frizzled, frzb lacks the 7 transmembrane domains normally found in G-protein-coupled receptors. It is still considered a homolog of frizzled because it contains a Cysteine Rich Domain (CRD), and because of its intracellular C-terminus which is crucial for signaling. The CRD is highly conserved in diverse proteins, such as receptor tyrosine kinases and functions as a

ligand binding domain In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...

. The C-terminal is a carboxyl terminus located intracellularly and is required for canonical signaling. The serpentine receptors (frzb) couple binds to ligand (Wnt protein) and activates G-proteins. A signal transduction cascade results in the secretion of first and second group

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

s. First group antagonists are composed of secreted Frizzled Related protein family (Sfrp) and Wnt inhibitory factor (Wif). Both Srfp and Wif bind directly to Wnt proteins blocking activation of the receptor. Second group of antagonists contains a class of Wnt inhibitory proteins known as Frizzled Receptor-like Proteins (FRPs). FRPs bind to the LRP (low-density-lipoprotein-related protein) co-receptors blocking activation of the

Wnt signaling pathway The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling ...

. One such pathway that involves Frizzled (Fz) family is the Wnt/

β-Catenin Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcrip ...

(β-Cat) signaling. β-Cat is an intracellular signal that is held in check by axin. In this pathway, the activation of Wnt receptors can be transduced by the canonical pathway via a series of

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

steps leading to stabilization and nuclear import of β-Cat into the nucleus where β-Cat associates with T-cell factor (TCF), a DNA-binding protein family. The β-Cat and TCF complex activates target genes of the Wnt pathway. In the absence of Wnt, β-Catenin is phosphorylated by complex containing GSK3 (glycogen synthase kinase 3) which targets β-Cat for proteosomal degradation. In the nucleus, members of the T-cell factor (TCF) family of DNA-binding proteins repress Wnt targets along with co-repressors such as Groucho (Gro). If Wnt is present it binds to Fz-LRP receptors causing axin to bind to intracellular domain of LRP and Fz. Dishevelled (Dvl) is a protein required for Wnt-dependent inhibition complex. The combination of LRP-axin induces Dvl phosphorylation (P) which blocks the APC-axin-GSK3 complex from phosphorylating β-Cat. The accumulated β-Cat then enters the nucleus and converts TCF into a transcriptional activator. Defects in Frzb are associated with female-specific osteoarthritis (OA) susceptibility which is the most prevalent form of arthritis and common cause of disability. https://web.archive.org/web/20070930043451/http://jcs.biologists.org/content/vol119/issue3/images/large/JCS02826F1.jpeg Frzb (known as Frzb1 or Sfrp3, Secreted Frizzled Related Protein 3) was initially identified as a chondrogenic factor during bone

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

, and was described as a novel marker of the

neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

-derived mesenchymal cells that contribute to dental follicle formation, the future periodontium.Thimios A. Mitsiadis, Pierfrancesco Pagella and Claudio Cantù. Early Determination of the Periodontal Domain by the Wnt-Antagonist Frzb/Sfrp3. Physiol., 21 November 2017 https://doi.org/10.3389/fphys.2017.0093

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External links

* {{Signaling proteins Signal transduction

See also

References

External links