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Fc receptors for immunoglobulins and their appearance during vertebrate evolution.

Akula S, Mohammadamin S, Hellman L - PLoS ONE (2014)

Bottom Line: These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish.In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance.Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Uppsala, Sweden.

ABSTRACT
Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

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The major Fc receptor gene loci in a panel of different vertebrates.Each horizontal line corresponds to a chromosome on which different Fc receptor genes are located. Genes are color coded. The Fc receptor-like (FcRL) genes are shown in yellow except the FcRLA and B that are in light green, classical IgG receptors in red (pseudogenes in striped red), IgE receptor in dark green, the IgM receptor in orange, the poly-Ig receptor (PIGR) and the IgA/IgM receptor in blue. The figure contains the genes identified for the following animal species: Zebrafish (Danio rerio), Western clawed frog (Xenopus silunarana and Xenopus tropicalis), Chicken (Gallus gallus), Turkey (Meleagris gallopovo), Zebra Finch (Taeniopygia guttata), Green anole (Anolis carolinennsis), Platypus (Ornithorhynchus anatinus), Opossum (Monodelphis domestica), Rat (Ratuus norvegius), Mouse (Mus musculus), Horse (Equus caballus), Rabbit (Oryctologus cunicullus), Pig (Sus scrofa), Dog (Canis lupus familaris), Cattle (Bos taurus), Orangutan (Pongo abelli), Chimpanzee (Pan troglodytes), Rhesus macaque (Macaca mulatta), Human (Homo sapiens).
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pone-0096903-g002: The major Fc receptor gene loci in a panel of different vertebrates.Each horizontal line corresponds to a chromosome on which different Fc receptor genes are located. Genes are color coded. The Fc receptor-like (FcRL) genes are shown in yellow except the FcRLA and B that are in light green, classical IgG receptors in red (pseudogenes in striped red), IgE receptor in dark green, the IgM receptor in orange, the poly-Ig receptor (PIGR) and the IgA/IgM receptor in blue. The figure contains the genes identified for the following animal species: Zebrafish (Danio rerio), Western clawed frog (Xenopus silunarana and Xenopus tropicalis), Chicken (Gallus gallus), Turkey (Meleagris gallopovo), Zebra Finch (Taeniopygia guttata), Green anole (Anolis carolinennsis), Platypus (Ornithorhynchus anatinus), Opossum (Monodelphis domestica), Rat (Ratuus norvegius), Mouse (Mus musculus), Horse (Equus caballus), Rabbit (Oryctologus cunicullus), Pig (Sus scrofa), Dog (Canis lupus familaris), Cattle (Bos taurus), Orangutan (Pongo abelli), Chimpanzee (Pan troglodytes), Rhesus macaque (Macaca mulatta), Human (Homo sapiens).

Mentions: Humans and mice have a complex set of Fc-specific receptors that match the number of different Ig-isotypes and subclasses (Figures 2 and 3). Four major types of classical Fc receptors for IgG: FcγRI, FcγRII, FcγRIII and FcγRIV, which show varying affinities for the four IgG isotypes, have been identified [18], [19]. Additionally, one high-affinity receptor for IgE (FcεRI), one for both IgM and IgA (FcαμR), one for IgM (FcμR) and one receptor for IgA (FcαRI) are found in almost all placental mammals studied [20]–[22]. The α chains of these receptors, which are the Ig-binding subunits, are all related in structure and it's likely they originate from one or a few common early ancestors via successive gene duplications [23]. In humans, all α chains of the IgG and IgE receptors have two extracellular Ig-like domains except for FcγRI, which contains three such domains. The opossum has recently been shown to have all of the classical IgG and IgE receptors except FcγRI, the high-affinity receptor for IgG, indicating that the two-domain receptors were the first to appear during mammalian evolution [24]. All of the IgG and IgE receptors, except one variant of FcγRIII in humans, FcγRIIIB, also have a transmembrane region that anchors the receptor in the membrane [18]. FcγRIIIB is a glycosylphosphatidylinositol (GPI) anchored activating receptor that has no cytoplasmic tail. In some of these receptors the cytoplasmic tail region is mediating the signal to the cell. However, for many of them the signaling function is found in another subunit of the receptor, the γ chain [25]. This non Ig-domain containing signaling subunit is a member of a small family of related molecules including the T-cell receptor (TCR) zeta chain, DAP10 and DAP12 [26]–[29]. The latter two proteins serve as signaling components of the NK cell receptor and related Ig-domain containing receptors [29]. The biological functions of the FcRs are regulated by immunoreceptor tyrosine-based activation motifs (ITAMs) and immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which activate or inhibit the cellular function, respectively [18], [20]. These motifs are located in the cytoplasmic part of the γ chain and in the case of FcγRIIB, in the cytoplasmic part of the α chain. FcRs with ITAMs elicit cell activation, endocytosis and phagocytosis, whereas receptors with ITIMs have an inhibitory effect on cell activation. The FcεRI also has a separate β chain, which most likely has a role in enhancing signaling, given it has one cytoplasmic ITAM motif [26]. The β chains show no homology to the α chains, are located on another chromosome, and are members of the MS4A family, which includes molecules like CD20, HTm4 and at least 18 other members in the human genome [30].


Fc receptors for immunoglobulins and their appearance during vertebrate evolution.

Akula S, Mohammadamin S, Hellman L - PLoS ONE (2014)

The major Fc receptor gene loci in a panel of different vertebrates.Each horizontal line corresponds to a chromosome on which different Fc receptor genes are located. Genes are color coded. The Fc receptor-like (FcRL) genes are shown in yellow except the FcRLA and B that are in light green, classical IgG receptors in red (pseudogenes in striped red), IgE receptor in dark green, the IgM receptor in orange, the poly-Ig receptor (PIGR) and the IgA/IgM receptor in blue. The figure contains the genes identified for the following animal species: Zebrafish (Danio rerio), Western clawed frog (Xenopus silunarana and Xenopus tropicalis), Chicken (Gallus gallus), Turkey (Meleagris gallopovo), Zebra Finch (Taeniopygia guttata), Green anole (Anolis carolinennsis), Platypus (Ornithorhynchus anatinus), Opossum (Monodelphis domestica), Rat (Ratuus norvegius), Mouse (Mus musculus), Horse (Equus caballus), Rabbit (Oryctologus cunicullus), Pig (Sus scrofa), Dog (Canis lupus familaris), Cattle (Bos taurus), Orangutan (Pongo abelli), Chimpanzee (Pan troglodytes), Rhesus macaque (Macaca mulatta), Human (Homo sapiens).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4016189&req=5

pone-0096903-g002: The major Fc receptor gene loci in a panel of different vertebrates.Each horizontal line corresponds to a chromosome on which different Fc receptor genes are located. Genes are color coded. The Fc receptor-like (FcRL) genes are shown in yellow except the FcRLA and B that are in light green, classical IgG receptors in red (pseudogenes in striped red), IgE receptor in dark green, the IgM receptor in orange, the poly-Ig receptor (PIGR) and the IgA/IgM receptor in blue. The figure contains the genes identified for the following animal species: Zebrafish (Danio rerio), Western clawed frog (Xenopus silunarana and Xenopus tropicalis), Chicken (Gallus gallus), Turkey (Meleagris gallopovo), Zebra Finch (Taeniopygia guttata), Green anole (Anolis carolinennsis), Platypus (Ornithorhynchus anatinus), Opossum (Monodelphis domestica), Rat (Ratuus norvegius), Mouse (Mus musculus), Horse (Equus caballus), Rabbit (Oryctologus cunicullus), Pig (Sus scrofa), Dog (Canis lupus familaris), Cattle (Bos taurus), Orangutan (Pongo abelli), Chimpanzee (Pan troglodytes), Rhesus macaque (Macaca mulatta), Human (Homo sapiens).
Mentions: Humans and mice have a complex set of Fc-specific receptors that match the number of different Ig-isotypes and subclasses (Figures 2 and 3). Four major types of classical Fc receptors for IgG: FcγRI, FcγRII, FcγRIII and FcγRIV, which show varying affinities for the four IgG isotypes, have been identified [18], [19]. Additionally, one high-affinity receptor for IgE (FcεRI), one for both IgM and IgA (FcαμR), one for IgM (FcμR) and one receptor for IgA (FcαRI) are found in almost all placental mammals studied [20]–[22]. The α chains of these receptors, which are the Ig-binding subunits, are all related in structure and it's likely they originate from one or a few common early ancestors via successive gene duplications [23]. In humans, all α chains of the IgG and IgE receptors have two extracellular Ig-like domains except for FcγRI, which contains three such domains. The opossum has recently been shown to have all of the classical IgG and IgE receptors except FcγRI, the high-affinity receptor for IgG, indicating that the two-domain receptors were the first to appear during mammalian evolution [24]. All of the IgG and IgE receptors, except one variant of FcγRIII in humans, FcγRIIIB, also have a transmembrane region that anchors the receptor in the membrane [18]. FcγRIIIB is a glycosylphosphatidylinositol (GPI) anchored activating receptor that has no cytoplasmic tail. In some of these receptors the cytoplasmic tail region is mediating the signal to the cell. However, for many of them the signaling function is found in another subunit of the receptor, the γ chain [25]. This non Ig-domain containing signaling subunit is a member of a small family of related molecules including the T-cell receptor (TCR) zeta chain, DAP10 and DAP12 [26]–[29]. The latter two proteins serve as signaling components of the NK cell receptor and related Ig-domain containing receptors [29]. The biological functions of the FcRs are regulated by immunoreceptor tyrosine-based activation motifs (ITAMs) and immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which activate or inhibit the cellular function, respectively [18], [20]. These motifs are located in the cytoplasmic part of the γ chain and in the case of FcγRIIB, in the cytoplasmic part of the α chain. FcRs with ITAMs elicit cell activation, endocytosis and phagocytosis, whereas receptors with ITIMs have an inhibitory effect on cell activation. The FcεRI also has a separate β chain, which most likely has a role in enhancing signaling, given it has one cytoplasmic ITAM motif [26]. The β chains show no homology to the α chains, are located on another chromosome, and are members of the MS4A family, which includes molecules like CD20, HTm4 and at least 18 other members in the human genome [30].

Bottom Line: These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish.In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance.Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Uppsala, Sweden.

ABSTRACT
Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

Show MeSH