CDB25:0003940 MBL2 — LRP1

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells.

The Journal of experimental medicine, 2001; PubMed, Homo sapiens MBL2 — Homo sapiens LRP1
ABSTRACT: Removal of apoptotic cells is essential for maintenance of tissue homeostasis, organogenesis, remodeling, development, and maintenance of the immune system, protection against neoplasia, and resolution of inflammation. The mechanisms of this removal involve recognition of the apoptotic cell surface and initiation of phagocytic uptake into a variety of cell types. Here we provide evidence that C1q and mannose binding lectin (MBL), a member of the collectin family of proteins, bind to apoptotic cells and stimulate ingestion of these by ligation on the phagocyte surface of the multifunctional protein, calreticulin (also known as the cC1qR), which in turn is bound to the endocytic receptor protein CD91, also known as the alpha-2-macroglobulin receptor. Use of these proteins provides another example of apoptotic cell clearance mediated by pattern recognition molecules of the innate immune system. Ingestion of the apoptotic cells through calreticulin/CD91 stimulation is further shown to involve the process of macropinocytosis, implicated as a primitive and relatively nonselective uptake mechanism for C1q- and MBL-enhanced engulfment of whole, intact apoptotic cells, as well as cell debris and foreign organisms to which these molecules may bind.

CD91 interacts with mannan-binding lectin (MBL) through the MBL-associated serine protease-binding site.

The FEBS journal, 2010; PubMed, Homo sapiens MBL2 — Homo sapiens LRP1
ABSTRACT: CD91 plays an important role in the scavenging of apoptotic material, possibly through binding to soluble pattern-recognition molecules. In this study, we investigated the interaction of CD91 with mannan-binding lectin (MBL), ficolins and lung surfactant proteins. Both MBL and L-ficolin were found to bind CD91. The MBL-CD91 interaction was time- and concentration-dependent and could be inhibited by known ligands of CD91. MBL-associated serine protease 3 (MASP-3) also inhibited binding between MBL and CD91, suggesting that the site of interaction is located at or near the MASP-MBL interaction site. This was confirmed by using MBL mutants deficient for MASP binding that were unable to interact with CD91. These findings demonstrate that MBL and L-ficolin interact with CD91, strongly suggesting that they have the potential to function as soluble recognition molecules for scavenging microbial and apoptotic material by CD91.
Basic Information on MBL2
Ligand Name: mannose binding lectin 2
Other Symbols: MBL, COLEC1, MBP-C, MBP1, MBP
Ligand Location: secreted based on perplexity, uniprot
HGNC Gene Symbol Report: MBL2
GeneCards: MBL2
HGNC Gene Group: Collectins, Complement system
Interactions with other Receptors for MBL2
Basic Information on LRP1
Receptor Name: LDL receptor related protein 1
Other Symbols: APR, A2MR, LRP, CD91, LRP1A, APOER, IGFBP3R1, IGFBP-3R
Receptor Location: cell membrane based on hpa, perplexity, uniprot
HGNC Gene Symbol Report: LRP1
GeneCards: LRP1