Identification of the Binding Domain for Secretory Phospholipases A2 on Their M-type 180-kDa Membrane Receptor

Nicolas, Jean-Paul; Lambeau, Gérard; Lazdunski, Michel

doi:10.1074/jbc.270.48.28869

Cited by 73 publications

(48 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Such a configuration must certainly sustain some functional implications in ligand binding. Taking our results together, with the data from others (2,3,31), we propose a model for the conformation of members of the MR superfamily in which the N-terminal end is bent to generate a globular head comprising several domains. In Endo180 and the MR, the extent of this globular region is determined by the specific CTLD to be functional in each receptor (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…Extensive work on Endo180 and the MR and PLA 2 R (6,19,26,31) has demonstrated that individual domains (CysR, FNII, and specific CTLDs) are necessary and sufficient to bind their specific ligands (sugars or collagens). Nevertheless, the fact that bent conformations are found under ligand binding conditions strongly suggests that such a configuration must have an important functional significance, and it might be important to regulate ligand recognition in their cellular con- (23) and they are highlighted with black arrows.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Boskovic

Arnold

Stilion

et al. 2006

Journal of Biological Chemistry

107

View full text Add to dashboard Cite

The mannose receptor family comprises four members in mammals, Endo180 (CD280), DEC-205 (CD205), phospholipase A 2 receptor (PLA 2 R) and the mannose receptor (MR, CD206), whose extracellular portion contains a similar domain arrangement: an N-terminal cysteine-rich domain (CysR) followed by a single fibronectin type II domain (FNII) and 8 -10 C-type lectin-like domains (CTLDs). These proteins mediate diverse functions ranging from extracellular matrix turnover through collagen uptake to homeostasis and immunity based on sugar recognition. Endo180 and the MR are multivalent transmembrane receptors capable of interacting with multiple ligands; in both receptors FNII recognizes collagens, and a single CTLD retains lectin activity (CTLD2 in Endo180 and CTLD4 in MR). It is expected that the overall conformation of these multivalent molecules would deeply influence their function as the availability of their binding sites could be altered under different conditions. However, conflicting reports have been published on the three-dimensional arrangement of these receptors. Here, we have used single particle electron microscopy to elucidate the three-dimensional organization of the MR and Endo180. Strikingly, we have found that both receptors display distinct threedimensional structures, which are, however, conceptually very similar: a bent and compact conformation built upon interactions of the CysR domain and the lone functional CTLD. Biochemical and electron microscopy experiments indicate that, under a low pH mimicking the endosomal environment, both MR and Endo180 experience large conformational changes. We propose a structural model for the mannose receptor family where at least two conformations exist that may serve to regulate differences in ligand selectivity.The mannose receptor (MR 4 and CD206), together with Endo180 (also known as the urokinase-type plasminogen activator receptor-associated protein (uPARAP) and CD280), the dendritic cell receptor DEC-205 (CD205) and the M-type phospholipase A 2 receptor (PLA 2 R) encompass the mannose receptor family of endocytic receptors (1, 2). The members of this family are unique within the superfamily of C-type lectins as these alone contain multiple C-type lectin-like domains (CTLDs) within a single polypeptide backbone. All these receptors are recycled between the plasma membrane and the endosomal apparatus and mediate the uptake of extracellular ligands for intracellular delivery (2). Recently, an avian structural homologue of the mammalian mannose receptor family members, FcRY, has been discovered to function as a yolk sac IgY receptor (3).The MR was originally described as a transmembrane receptor that recognized saccharide chains terminating in mannose and designated as the macrophage mannose receptor. Since its expression was found not to be restricted to macrophages, it is now known as MR (2). MR executes important roles in the immune system by functioning as a pattern recognition receptor toward a wide range of pathogens. Other members of the family were found ...

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Boskovic

Arnold

Stilion

et al. 2006

Journal of Biological Chemistry

107

View full text Add to dashboard Cite

show abstract

“…The different dose-response curves of group IA sPLA 2 , active on both the M-type and the N-type, and group IIA sPLA 2 , active only on the M-type, suggest that both receptors may be present on human macrophages. The M-type receptor has been included in a family of lectin-binding receptors (61), including the mannose receptor, uniquely expressed on macrophages (44), and the DEC-205, expressed on dendritic cells (62). mp-BSA, which is a ligand of the mannose receptor, induces ␤-glucuronidase release quantitatively similar to that induced by group IIA sPLA 2 .…”

Section: Discussionmentioning

confidence: 99%

Secretory Phospholipases A2 Induce β-Glucuronidase Release and IL-6 Production from Human Lung Macrophages

Triggiani

Granata

Oriente

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Secretory phospholipases A2 (sPLA2s) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA sPLA2 has been detected in inflammatory fluids, and its plasma level is increased in inflammatory diseases. To investigate a potential mechanism of sPLA2-induced inflammation we studied the effect of group IA (from cobra venom) and group IIA (human synovial) sPLA2s on human macrophages. Both sPLA2s induced a concentration- and Ca2+-dependent, noncytotoxic release of β-glucuronidase (16.2 ± 2.4% and 13.1 ± 1.5% of the total content with groups IA and IIA, respectively). Both sPLA2s also increased the rate of secretion of IL-6 and enhanced the expression of IL-6 mRNA. Preincubation of macrophages with inhibitors of the hydrolytic activity of sPLA2 or cytosolic PLA2 did not influence the release of β-glucuronidase. Incubation of macrophages with p-aminophenyl-mannopyranoside-BSA (mp-BSA), a ligand of the mannose receptor, also resulted in β-glucuronidase release. However, while preincubation of macrophages with mp-BSA had no effect on β-glucuronidase release induced by group IIA sPLA2, it enhanced that induced by group IA sPLA2. A blocking Ab anti-mannose receptor inhibited both mp-BSA- and group IIA-induced β-glucuronidase release. Taken together, these data indicate that group IA and IIA sPLA2s activate macrophages with a mechanism independent from their enzymatic activities and probably related to the activation of the mannose receptor or sPLA2-specific receptors. The secretion of enzymes and cytokines induced by sPLA2s from human macrophages may play an important role in inflammation and tissue damage associated with the release of sPLA2s.

show abstract

“…It also binds pancreatic type and inflammatory type sPLA 2 s with high affinities (1-10 nM), suggesting that these sPLA 2 s are probably the endogenous ligands of this sPLA 2 receptor (21). The M-type receptor has been cloned recently from various animal species (21)(22)(23)(24), and its molecular properties have been analyzed in detail (23,(25)(26)(27)(28)(29). Notably, the interaction between the M-type receptor and sPLA 2 has been studied both from the receptor side (25,29) and from the sPLA 2 side to show that the Ca 2ϩ -binding loop of the sPLA 2 ligand plays a central role in binding to M-type receptor (28).…”

mentioning

confidence: 99%

Localization of Structural Elements of Bee Venom Phospholipase A2 Involved in N-type Receptor Binding and Neurotoxicity

Nicolas

Lin

Lambeau

et al. 1997

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

We have shown previously that neurotoxic venom secretory phospholipases A 2 (sPLA 2 s) have specific receptors in brain membranes called N-type receptors that are likely to play a role in the molecular events leading to neurotoxicity of these proteins. The sPLA 2 found in honey bee venom is neurotoxic and binds to this receptor with high affinity. In this paper, we have used a number of mutants of bee venom sPLA 2 produced in Escherichia coli to determine the structural elements of this protein that are involved in its binding to N-type receptors. Mutations in the interfacial binding surface, in the Ca 2؉ -binding loop and in the hydrophobic channel lead to a dramatic decrease in binding to N-type receptors, whereas mutations of surface residues localized in other parts of the sPLA 2 structure do not significantly modify the binding properties. Neurotoxicity experiments show that mutants with low affinity for N-type receptors are devoid of neurotoxic properties, even though some of them retain high enzymatic activity. These results provide further evidence for the involvement of N-type receptors in neurotoxic processes associated with venom sPLA 2 s and identify the surface region surrounding the hydrophobic channel of bee venom sPLA 2 as the N-type receptor recognition domain.

show abstract

Identification of the Binding Domain for Secretory Phospholipases A2 on Their M-type 180-kDa Membrane Receptor

Cited by 73 publications

References 46 publications

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Secretory Phospholipases A2 Induce β-Glucuronidase Release and IL-6 Production from Human Lung Macrophages

Localization of Structural Elements of Bee Venom Phospholipase A2 Involved in N-type Receptor Binding and Neurotoxicity

Contact Info

Product

Resources

About