Frizzled
Encyclopedia
Frizzled is a family of G protein-coupled receptor
proteins that serve as receptors in the Wnt signaling pathway
and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled
in the cytosol.
, the clear fluid inside the eye.
The frizzled (fz) locus of Drosophila
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
, 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.
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
proteins that serve as receptors in the Wnt signaling pathway
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled
Dishevelled
Dishevelled is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors...
in the cytosol.
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. Mutations in the human frizzled-4 receptor have been linked to familial exudative vitreoretinopathy, a rare disease affecting the retina at the back of the eye, and the vitreousVitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...
, the clear fluid inside the eye.
The frizzled (fz) locus of Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
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. In Drosophila melanogasterDrosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
, 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-1FZD1Frizzled-1 is a protein that in humans is encoded by the FZD1 gene.-Further reading:...
- Frizzled-2FZD2Frizzled-2 is a protein that in humans is encoded by the FZD2 gene.-Further reading:...
- Frizzled-3FZD3Frizzled-3 is a protein that in humans is encoded by the FZD3 gene.-Further reading:...
- Frizzled-4FZD4Frizzled-4 is a protein that in humans is encoded by the FZD4 gene. FZD4 has also been designated as CD344 .-External links:]*...
- Frizzled-5FZD5Frizzled-5 is a protein that in humans is encoded by the FZD5 gene.-Further reading:...
- Frizzled-6FZD6Frizzled-6 is a protein that in humans is encoded by the FZD6 gene.Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD6 protein contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region,...
- Frizzled-7FZD7Frizzled-7 is a protein that in humans is encoded by the FZD7 gene.-Further reading:...
- Frizzled-8FZD8Frizzled-8 is a protein that in humans is encoded by the FZD8 gene.-Further reading:...
- Frizzled-9FZD9Frizzled-9 is a protein that in humans is encoded by the FZD9 gene. FZD9 has also been designated as CD349 .-External links:...
- Frizzled-10FZD10Frizzled-10 is a protein that in humans is encoded by the FZD10 gene. FZD10 has also been designated as CD350 .-External links:...