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.