IndraLab

"The cytoplasmic calreticulin binds to phosphatidylserine in the inner leaflet of the plasma membrane from where it is externalized as the plasma membrane loses its asymmetry."

"The second suggested pathway, relevant to apoptotic cells, involves the binding of cytosolic calreticulin to phosphatidylserine on the inner leaflet of the plasma membrane prior to apoptotic exposure of phosphatidylserine-calreticulin complexes on the cell surface ( xref )."

"Calreticulin can bind phosphatidylserine ( xref ), and so may signal to phagocytes either alone or in association with exposed phosphatidylserine."

"Once externalized, CALR binds to phosphatidylserine and functions as a damage-associated molecular pattern (DAMP), thereby promoting macrophage-mediated phagocytosis [ xref ]."

"Calreticulin can bind in a Ca 2+ -dependent manner to phosphatidylserine (PS) with high affinity (K D = 1.5 × 10 −5 M) [ xref , xref ]."

"CALR associates with phosphatidylserine (PS) in a Ca 2+ -dependent manner and both are translocated as punctate clusters on the cell surface [39] ."

"Calreticulin binds to phosphatidylserine on the surface of apoptotic cells via a calcium and C-domain-dependent pathway and with phagocytes via lectin and P-domain-dependent interaction that may involve its generic polypeptide-binding site ( xref ) ( xref )."

"During ICD, CALR that is bound to phosphatidylserine on the plasma membrane is exposed extracellularly. xref Classically, CALR mediates phagocytosis of cells through direct binding between stressed, damaged cells and phagocytic leukocytes and induces inflammatory responses. xref , xref Although it does not induce phagocytosis, unbound CALR similarly induces inflammatory immune responses and activates inflammatory T helper cells. xref , xref , xref , xref Hsp70 activates infiltrating natural killer cells and T lymphocytes within tumors, binds to Toll-like receptors on macrophages that release pro-inflammatory cytokines, and fused with antigens has produced cancer vaccines. xref , xref , xref , xref Gp96 activates pro-inflammatory macrophages and antigen-presenting cells (APCs) within tumors and has also been developed as a cancer peptide vaccine that became the first therapeutic cancer vaccine to win regulatory approval anywhere in the world. xref , xref , xref HMGB1 is released by necrotic tumor cells, induces inflammatory macrophages that secrete cytokines and pro-infiltration molecules, and activates infiltrating dendritic cells (DCs) that present tumor antigens. xref , xref , xref , xref , xref "

"Calreticulin can bind phosphatidylserine ( xref ), and Wijeyesakere et al. ( xref ) showed that calreticulin directly bound phosphatidylserine exposed on apoptotic cells via its C-terminal acidic region, and enhanced phagocytosis of apoptotic fibroblasts by peritoneal macrophages, which was dependent on this phosphatidylserine-binding region."