Frizzled is a family of atypical

G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

that serve as receptors in 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 p ...

and other signaling pathways. When activated, Frizzled leads to activation of

Dishevelled Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh (Dvl in mammals) is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initi ...

in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

Species distribution

Frizzled proteins and the genes that encode them have been identified in an array of animals, from sponges to humans.

Function

Frizzled proteins also play key roles in governing cell polarity, embryonic development, formation of neural synapses, cell proliferation, and many other processes in developing and adult organisms. These processes occur as a result of one of three signaling pathways. These include the canonical Wnt/β-catenin pathway, Wnt/calcium pathway, and planar cell polarity (PCP) pathway. Mutations in the human frizzled-4 receptor have been linked to

familial exudative vitreoretinopathy Familial exudative vitreoretinopathy (FEVR, pronounced as fever) is a genetic disorder affecting the growth and development of blood vessels in the retina of the eye. This disease can lead to visual impairment and sometimes complete blindness in o ...

, a rare disease affecting the retina at the back of the eye, and the vitreous, the clear fluid inside the eye. The frizzled (fz) locus of

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

coordinates the cytoskeletons of epidermal cells, producing a parallel array of cuticular hairs and bristles. In fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the wild-type wing, all hairs point towards the distal tip. In the developing wing, Fz has 2 functions: it is required for the proximal-distal transmission of an intracellular polarity signal; and it is required for cells to respond to the polarity signal. Fz produces an mRNA that encodes an integral membrane protein with 7 putative transmembrane (TM) domains. This protein should contain both extracellular and cytoplasmic domains, which could function in the transmission and interpretation of polarity information. This signature is usually found downstream of the Fz domain ()

Cysteine-rich domain

Frizzled proteins include cysteine-rich domain that is conserved in diverse proteins, including several

receptor tyrosine kinases Receptor tyrosine kinases (RTKs) are the high- affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinas ...

. 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 Ch ...

'', members of the Frizzled family of tissue-polarity genes encode proteins that appear to function as cell-surface receptors for Wnts. The Frizzled genes belong to the seven transmembrane class of receptors (7TMR) and have in their extracellular region a cysteine-rich domain that has been implicated as the Wnt binding domain. Sequence similarity between the cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which have roles in development, include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal-specific kinase (NSK2), and ROR1 and ROR2. The structure of this domain is known and is composed mainly of alpha helices. This domain contains ten conserved cysteines that form five disulphide bridges.

Group members

The following is a list of the ten known human frizzled receptors: * Frizzled-1 () * Frizzled-2 () * Frizzled-3 () * Frizzled-4 () * Frizzled-5 () * Frizzled-6 () * Frizzled-7 () * Frizzled-8 () * Frizzled-9 () * Frizzled-10 ()

As a drug target

Vantictumab Vantictumab is a human IgG2 monoclonal antibody designed for the treatment of cancer. This drug was developed by OncoMed, OncoMed Pharmaceuticals Inc. in partnership with Bayer. OncoMed was awarded a patent in 2016, which is set to expire in 202 ...

is a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

against five frizzled receptors that is under development for the treatment of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

References

External links

* * {{Wnt signaling pathway G protein-coupled receptors