Involvement of the chemokine-like receptor GPR33 in innate immunity.
Chemokine receptors control leukocyte chemotaxis and cell-cell communication but have also been associated with pathogen entry. GPR33, an orphan member of the chemokine-like receptor family, is a pseudogene in most humans. After the appearance of GPR33 in first mammalian genomes, this receptor underwent independent pseudogenization in humans, other hominoids and some rodent species. It was speculated that a likely cause of GPR33 inactivation was its interplay with a rodent-hominoid-specific pathogen. Simultaneous pseudogenization in several unrelated species within the last 1 million years (myr) caused by neutral drift appears to be very unlikely suggesting selection on the GPR33 null-allele. Although there are no signatures of recent selection on human GPR33 we found a significant increase in the pseudogene allele frequency in European populations when compared with African and Asian populations. Because its role in the immune system was still hypothetical expression analysis revealed that GPR33 is highly expressed in dendritic cells (DC). Murine GPR33 expression is regulated by the activity of toll-like receptors (TLR) and AP-1/NF-kappaB signaling pathways in cell culture and in vivo. Our data indicate an important role of GPR33 function in innate immunity which became dispensable during human evolution most likely due to past or balancing selection.
Bohnekamp
Jens
J
Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
Böselt
Iris
I
Saalbach
Anja
A
Tönjes
Anke
A
Kovacs
Peter
P
Biebermann
Heike
H
Manvelyan
Hovhannes M
HM
Polte
Tobias
T
Gasperikova
Daniela
D
Lkhagvasuren
Sodnomtsogt
S
Baier
Leslie
L
Stumvoll
Michael
M
Römpler
Holger
H
Schöneberg
Torsten
T
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011544:Pseudogenes / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
C504823:GPR33 protein, human; C114478:Gpr33 protein, mouse; D043562:Receptors, G-Protein-Coupled; D051193:Toll-Like Receptors
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