Molecular characterization of the murine SIGNR1 gene encoding a C-type lectin homologous to human DC-SIGN and DC-SIGNR.
The C-type lectin human dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin (DC-SIGN) plays important roles in pattern recognition by dendritic cells in the immune system. In addition to binding human immunodeficiency virus (HIV), this type II membrane protein binds with high affinity to the adhesion molecules ICAM-3 and -2 to promote important dendritic cell interactions with naive T cells and endothelial cells, respectively. DC-SIGNR, a human DC-SIGN homologue expressed on sinusoidal endothelial cells in liver and lymph node, also binds and transmits HIV virus. We describe the cloning and characterization of a family of murine complementary DNAs (cDNAs) called SIGNR1, expressed in skin and spleen, that encode C-type lectins highly related to human DC-SIGN and DC-SIGNR. We also report the genomic structure of the SIGNR1 gene and compare it to that of human DC-SIGN and DC-SIGNR. The different transcripts (alpha, beta, gamma, delta) are generated by differences in 5' untranslated sequences, alternative splicing and/or the use of different polyadenylation sites. The predicted open reading frames encoded by the cDNAs are most closely related to human DC-SIGN and DC-SIGNR in the cytoplasmic domain, the transmembrane region and the carbohydrate recognition domain. Moreover, the alternatively spliced transcripts encode proteins that lack the transmembrane region or have modified carbohydrate recognition domains. Northern hybridization experiments with several different SIGNR1 cDNA probes reveal transcripts of 1.3 and 2.1 kb that are expressed in a tissue-restricted fashion in murine skin, spleen and lung. In situ hybridization and immunocytochemistry experiments demonstrate that, like human DC-SIGN, the murine messenger RNAs are expressed in subsets of dendritic cells in the spleen and skin.
Parent
Stephen A
SA
Department of Immunology and Rheumatology, Merck Research Laboratories, PO Box 2000, RY 80Y-225, Rahway, NJ 07065, USA. steve_parent@merck.com
Zhang
Theresa
T
Chrebet
Gary
G
Clemas
Joseph A
JA
Figueroa
David J
DJ
Ky
Betty
B
Blevins
Richard A
RA
Austin
Christopher P
CP
Rosen
Hugh
H
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D037102:Lectins / Q000235:genetics*; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D037102:Lectins; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human