Stabilin-1, a homeostatic scavenger receptor with multiple functions.
The multifunctional scavenger receptor stabilin-1 (STAB1, FEEL-1, CLEVER-1, KIAA0246) was originally identified as the MS-1 antigen, expressed by sinusoidal endothelial cells in human spleen. Extensive histological studies revealed that stabilin-1 is also expressed by tissue macrophages and sinusoidal endothelial cells in the healthy organism; its expression on both macrophages and different subtypes of endothelial cells is induced during chronic inflammation and tumorigenesis. In vitro induction of stabilin-1 in macrophages requires the presence of glucocorticoids. Stabilin-1 is involved in two intracellular trafficking pathways: receptor mediated endocytosis and recycling; and shuttling between the endosomal compartment and trans-Golgi network (TGN). The latter intracellular pathway of stabilin-1 trafficking is mediated by GGAs, clathrin adaptors that interact with the DDSLL motif in the cytoplasmic tail of stabilin-1. When expressed by alternatively activated macrophages, stabilin-1 mediates the uptake and targeting for degradation of acLDL and SPARC, a regulator of tissue remodeling. Likewise, stabilin-1 in macrophages is involved in intracellular sorting and lysosomal delivery of the novel stabilin- 1-interacting chitinase-like protein (SI-CLP). Indirect evidence suggests that stabilin-1 is involved in adhesion and transmigration in various cell types (including tumor cells, leukocytes, and lymphocytes); however, its rapid recycling and scant level of surface expression argue against its universal role in cell adhesion. In summary, stabilin-1 is a homeostatic receptor which links signals from the extracellular environment to intracellular vesicular processes, creating a potential impact on the macrophage secretion profile.
Kzhyshkowska
Julia
J
Department of Dermatology, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, D-68167 Mannheim, Germany. julia.kzhyshkowska@haut.ma.uni-heidelberg.de
Gratchev
A
A
Goerdt
S
S
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism* / Q000502:physiology*; D002469:Cell Separation; D004705:Endocytosis; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism* / Q000502:physiology*; D051116:Receptors, Scavenger / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D008024:Ligands; D008077:Lipoproteins, LDL; D016201:Receptors, Lymphocyte Homing; D051116:Receptors, Scavenger; C449926:STAB1 protein, human