The role of phosphatidylserine recognition receptors in multiple biological functions

Abstract

Apoptotic cells are rapidly engulfed and degraded by phagocytes through efferocytosis. Efferocytosis is a highly regulated process. It is triggered upon the activation of caspase-dependent apoptosis, which in turn promotes the expression of "eat me" signals on the surface of dying cells and the release of soluble "find me" signals for the recruitment of phagocytes. To date, many "eat me" signals have been recognized, including phosphatidylserine (PS), intercellular adhesion molecule-3, carbohydrates (e.g., amino sugars, mannose) and calreticulin. Among them, PS is the most studied one. PS recognition receptors are different functionally active receptors expressed by phagocytes. Various PS recognition receptors with different structure, cell type expression, and ability to bind to PS have been recognized. Although PS recognition receptors do not fall into a single classification or family of proteins due to their structural differences, they all share the common ability to activate downstream signaling pathways leading to the production of anti-inflammatory mediators. In this review, available evidence regarding molecular mechanisms underlying PS recognition receptor-regulated clearance of apoptotic cells is discussed. In addition, some efferocytosis-independent biological functions of PS recognition receptors are reviewed.

Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell

“…When an apoptotic stimulus occurs, the cells begin to externalize phosphatidylserine, which is normally located in the inner plasma membrane. It works as a signal for phagocytes to carry out efferocytosis, removal of apoptotic cell bodies from the body [ 55 ].…”

Flagging fusion: Phosphatidylserine signaling in cell–cell fusion

“… P4-ATPases of the ATP 8, 9, 10, and 11 families Flip PS from the exofacial to the cytofacial leaflet of the PM ( 61 ) Myoblasts ( 169 ) ABC transporter CED-7 Elicits PS exposure on axon PMs in C. elegans ( 194 ) Axon regeneration ( 127 ) PLSCRs May play some role in eliciting PS exposure ( 79 , 81 ) Viral entry ( 82 ) PS recognizing machinery Annexins Soluble, PS-binding proteins that function as assembly factors in many biological processes ( 195 ) Myoblasts ( 21 , 196 ), trophoblasts ( 167 ), osteoclasts ( 22 ) Lactadherin Soluble, PS-binding protein ( 197 ) Sperm-egg ( 168 ) Protein S Soluble, PS-binding protein ( 198 ) ? GAS-6 Soluble, PS-binding protein ( 177 ) Viral entry ( 199 ) CD300 receptors Membrane-bound receptors with affinity for exofacial lipids, some specifically bind PS ( 200 ) Viral entry ( 201 ) TIM receptors 1 and 4 Membrane-bound PS receptors with major roles in immunity ( 202 ) Viral entry ( 203 ) BAI receptors 1 and 3 Membrane-bound PS receptors ( 204 ) Myoblasts ( 162 ) Stabilin 2 Membrane-bound PS receptor ( 205 ) Myoblasts ( ...…”

Efferocytosis Mediated Modulation of Injury after Neonatal Brain Hypoxia-Ischemia

“…Efferocytes respond to multiple stimuli in the injured environment. Yet, efferocytes must recognize dead cells exhibiting “find me” signals that differ depending on the tissue and type of injury [ 40 ] (e.g., lysophosphatidylcholine—LPC, sphingosine-1-phosphate—S1P, CX3C motif chemokine ligand 1—CX3CL1, nucleotides adenosine triphosphate—ATP and uridine triphosphate—UTP) [ 41 , 42 , 43 , 44 ] and “eat me” signals (phosphatidylserine—PtdSer, calreticulin—Calr, intracellular adhesion molecule 3—ICAM3) [ 45 , 46 , 47 , 48 ] from distressed cells that release “help me” signals (interleukin-34, fibroblast growth factor 2, lipocalin-2) [ 49 ] and healthy cells with “don’t eat me” signals (CD31, CD47) [ 45 , 50 ]. Interestingly, some cells secrete “keep out signals”, for example, lactoferrin to selectively exclude certain efferocytes, such as eosinophils or neutrophils [ 45 , 51 ] underlying the cellular specificity of the efferocytosis process ( Figure 1 ).…”