CDB15:0000177 CALR — LRP1

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

Title

Journal:; Year Published:

Abstract

Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.

Cell, 2005; PubMed, Mus Musculus Calr — Mus Musculus Lrp1

ABSTRACT: Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where "don't eat me" signals are rendered inactive and "eat me" signals, including calreticulin and phosphatidylserine, congregate together and signal for removal.

CD91-dependent programming of T-helper cell responses following heat shock protein immunization.

Nature communications, 2011; PubMed, Mus Musculus Calr — Mus Musculus Lrp1

ABSTRACT: The immunogenic heat shock proteins (HSPs) gp96, hsp70 and calreticulin (CRT) bind to CD91 on antigen-presenting cells (APCs) for cross-presentation of the HSP-chaperoned peptides. This event leads to priming of T-cell responses. Here we show that CD91 serves as a signalling receptor for these HSPs, allowing for the maturation of APCs, secretion of cytokines and priming of T-helper (Th) cells. Specifically, CD91 is phosphorylated in response to HSPs in a unique pattern and phospho-CD91 triggers signalling cascades to activate nuclear factor-kappa B. Each HSP-CD91 interaction on APCs stimulates a unique cytokine profile, which dictates priming of specific Th cell subsets. Thus, in a transforming growth factor-β tumour microenvironment, immunization with CRT, but not gp96 or hsp70, primes Th17-cell responses in a CD91-dependent manner. These results are important for development of T-cell responses in situ in tumour-bearing hosts and for vaccination against cancer and infectious disease.

Macrophage expression of LRP1, a receptor for apoptotic cells and unopsonized erythrocytes, can be regulated by glucocorticoids.

Biochemical and biophysical research communications, 2012; PubMed, Mus Musculus Calr — Mus Musculus Lrp1

ABSTRACT: Macrophage phagocytosis of apoptotic cells, or unopsonized viable CD47(-/-) red blood cells, can be mediated by the interaction between calreticulin (CRT) on the target cell and LDL receptor-related protein-1 (LRP1/CD91/α2-macroglobulin receptor) on the macrophage. Glucocorticoids (GC) are powerful in treatment of a range of inflammatory conditions, and were shown to enhance macrophage uptake of apoptotic cells. Here we investigated if the ability of GC to promote macrophage uptake of apoptotic cells could in part be mediated by an upregulation of macrophage LRP1 expression. Using both resident peritoneal and bone marrow-derived macrophages, we found that the GC dexamethasone could dose- and time-dependently increase macrophage LRP1 expression. The GC receptor-inhibitor RU486 could dose-dependently prevent LRP1 upregulation. Dexamethasone-treated macrophages did also show enhanced phagocytosis of apoptotic thymocytes as well as unopsonized viable CD47(-/-) red blood cells, which was sensitive to inhibition by the LRP1-agonist RAP. In conclusion, these data suggest that GC-stimulated macrophage uptake of apoptotic cells may involve an upregulation of macrophage LRP1 expression and enhanced LRP1-mediated phagocytosis.

Basic Information on CALR

Ligand Name: calreticulin

Other Symbols: RO, SSA, cC1qR, CRT, FLJ26680, CALR1

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: CALR

GeneCards: CALR

HGNC Gene Group: MicroRNA host genes

Functional Annotations for CALR

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for CALR

CALR — SCARF1

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

HGNC Gene Group: MicroRNA host genes, CD molecules, Low density lipoprotein receptors

Functional Annotations for LRP1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for LRP1

A2M — LRP1 ・ APOE — LRP1 ・ APP — LRP1 ・ C1QB — LRP1 ・ C3 — LRP1 ・ C4BPA — LRP1 ・ CCN2 — LRP1 ・ F8 — LRP1 ・ F9 — LRP1 ・ FCN2 — LRP1 ・ HSP90B1 — LRP1 ・ LIPC — LRP1 ・ LPL — LRP1 ・ LRPAP1 — LRP1 ・ LTF — LRP1 ・ MDK — LRP1 ・ MMP13 — LRP1 ・ MMP9 — LRP1 ・ PDGFB — LRP1 ・ PLAT — LRP1 ・ PLAU — LRP1 ・ PSAP — LRP1 ・ SERPINA1 — LRP1 ・ SERPINC1 — LRP1 ・ SERPINE1 — LRP1 ・ SERPINE2 — LRP1 ・ SERPING1 — LRP1 ・ TFPI — LRP1 ・ THBS1 — LRP1 ・ ADAMTS1 — LRP1 ・ APOC3 — LRP1 ・ C1QA — LRP1 ・ CCN1 — LRP1 ・ CEMIP — LRP1 ・ HGFAC — LRP1 ・ HMGB1 — LRP1 ・ HMGB2 — LRP1 ・ HPX — LRP1 ・ HSP90AA1 — LRP1 ・ HSPA1A — LRP1 ・ HSPA4 — LRP1 ・ IGFBP7 — LRP1 ・ LIF — LRP1 ・ MBL2 — LRP1 ・ MMP1 — LRP1 ・ PF4 — LRP1 ・ PLAUR — LRP1 ・ SERPIND1 — LRP1 ・ SFTPA1 — LRP1 ・ SFTPD — LRP1 ・ SLIT2 — LRP1 ・ SPARC — LRP1 ・ TIMP1 — LRP1 ・ TIMP3 — LRP1 ・ TNFAIP6 — LRP1 ・ VWF — LRP1