An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors.

Freeman, Mason W.; Ashkenas, John; Rees, D. J. G.; Kingsley, David M.; Copeland, Neal G.; Jenkins, Nancy A.; Krieger, Monty

doi:10.1073/pnas.87.22.8810

Cited by 270 publications

(156 citation statements)

References 36 publications

Supporting

Mentioning

151

Contrasting

Order By: Relevance

“…This substitution was initially considered type II specific [6], further evidence suggesting however the possibility of polymorphism of a single gene transcript [11,32]. Hphl digestion of the 626 bp amplified fragment, obtained with the BTSCAVRP2 and BTSCAVRM2 primers, produced three fragments of 507, 81 and 38 bp, as expected from the presence of a T at nucleotide 750 (Fig.…”

Section: Btscavrm2bmentioning

confidence: 83%

Expression of receptors for native and chemically modified low‐density lipoproteins in brain microvessels

et al. 1997

View full text Add to dashboard Cite

Despite the importance of cholesterol metabolism in the central nervous system, only relatively few studies have dealt with the cerebral uptake and transport of lipids into the brain compartment. These functions are mediated by the endothelium of brain microvessels, which forms the anatomical basis of the blood-brain barrier. By a reverse transcriptase PCR study of messenger RNA expression we could show, in bovine brain microvessels, the presence of transcripts of native low-density lipoprotein receptor and of both type I and II scavenger receptors. Brain microvessels therefore appear to play an active role in the uptake of native and modified low-density lipoproteins.

show abstract

Section: Btscavrm2bmentioning

confidence: 83%

Expression of receptors for native and chemically modified low‐density lipoproteins in brain microvessels

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Which cysteine-rich proteins could become exposed on the cell surface early in apoptosis is unknown, but ecto-calreticulin has been proposed possibly in association with a protein disulfide isomerase of the endoplasmic reticulum [38]. Some macrophage SRs such as SR-A1, MARCO, CD-163, and SP α belong to the scavenger receptor cysteine-rich superfamily (SRCR-SF), a conserved family of receptors containing one or more repeats of a cysteine-rich extracellular domain containing six to eight cysteines arranged in a disulfide-bonded pattern [39]. The macrophage P2X7 receptor may be related to this scavenger superfamily but has developed a divergent role in the recognition and removal of apoptotic cells in the absence of extracellular ATP and serum.…”

Section: Autofluorescence P2x7-ed Controlmentioning

confidence: 99%

A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP

Wiley

2012

Purinergic Signalling

View full text Add to dashboard Cite

The P2X7 receptor is widely recognized to mediate the proinflammatory effects of extracellular ATP. However this receptor in the absence of ATP may have a function unrelated to inflammation. Our data show that P2X7 expressed on the surface of monocyte/macrophages or on epithelial HEK-293 cells greatly augments the engulfment of latex beads and live and heat-killed bacteria by effector phagocyte in the absence of ATP and serum. The expression of P2X7 on the effector also confers the ability to phagocytose apoptotic target cells and an accumulation of P2X7 can be seen at the attachment point to the target. Activation of the P2X7 receptor by ATP causes a slow dissociation (over 10-15 min) of nonmuscle myosin from the P2X7 membrane complex and abolishes further P2X7-mediated phagocytosis of these targets. The recent crystal structure of the homologous zebrafish P2X4 receptor shows an exposed "nose" of the ectodomain (residues 115-162) which contains three of the five disulfide bonds conserved in all P2X receptors. Three short biotin-labeled peptides mimicking sequence of this exposed region bound to apoptotic target cells but not to either viable cells or to other target particles. All three peptides contained one or two cysteine residues and their replacement by alanine abolished peptide binding. These data implicate thiol-disulfide exchange reactions in the initial tethering of apoptotic cells to macrophage and establish P2X7 as one of the scavenger receptors involved in the recognition and removal of apoptotic cells in the absence of extracellular ATP and serum.

show abstract

“…is an ancient and highly conserved family of proteins, characterized by the presence of one or several repeats of a cysteinerich extracellular domain named SRCR (1,2). The SRCR-SF includes both cell-surface and secreted proteins that can be expressed on cells of hemopoietic origin such as macrophages (e.g., SR-AI/II, MARCO, CD163, Mac2-binding protein, and Sp␣) and lymphocytes (e.g., CD5, CD6, and T19/WT1), as well as on nonhematological cells such as those from of the digestive, respiratory, and urinary epithelial tracts (e.g., DMBT1, S4D-SRCRB, and SCARA5) (2).…”

Section: T He Scavenger Receptor Cysteine-rich Superfamily (Srcr-sf)mentioning

confidence: 99%

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

Sarrias

Farnós

Mota

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

101

118

View full text Add to dashboard Cite

CD6 is a lymphocyte receptor that belongs to the scavenger receptor cysteine-rich superfamily. Because some members of the scavenger receptor cysteine-rich superfamily act as pattern recognition receptors for microbial components, we studied whether CD6 shares this function. We produced a recombinant form of the ectodomain of CD6 (rsCD6), which was indistinguishable (in apparent molecular mass, antibody reactivity, and cell binding properties) from a circulating form of CD6 affinity-purified from human serum. rsCD6 bound to and aggregated several Gram-positive and -negative bacterial strains through the recognition of lipoteichoic acid and LPS, respectively. The K d of the LPS-rsCD6 interaction was 2.69 ؎ 0.32 ؋ 10 ؊8 M, which is similar to that reported for the LPS-CD14 interaction. Further experiments showed that membrane CD6 also retains the LPS-binding ability, and it results in activation of the MAPK signaling cascade. In vivo experiments demonstrated that i.p. administration of rsCD6 before lethal LPS challenge significantly improved mice survival, and this was concomitant with reduced serum levels of the proinflammatory cytokines TNF-␣, IL6, and IL-1␤. In conclusion, our results illustrate the unprecedented bacterial binding properties of rsCD6 and support its therapeutic potential for the intervention of septic shock syndrome or other inflammatory diseases of infectious origin.bacterial cell component ͉ innate immunity ͉ lymphocyte surface receptor

show abstract

An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors.

Cited by 270 publications

References 36 publications

Expression of receptors for native and chemically modified low‐density lipoproteins in brain microvessels

Expression of receptors for native and chemically modified low‐density lipoproteins in brain microvessels

A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

Contact Info

Product

Resources

About