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A novel GGA-binding site is required for intracellular sorting mediated by stabilin-1.
Mol. Cell. Biol. 29, 6097-6105 (2009)
Stabilin-1 is a unique scavenger receptor that combines endocytic and intracellular sorting functions in macrophages. Stabilin-1 mediates the endocytosis of acetylated low-density lipoprotein (acLDL), SPARC, and growth hormone family member placental lactogen (PL). At the same time, stabilin-1 is involved in trans-Golgi network-to-endosome routing of the endogenous chitinase-like protein SI-CLP (stabilin-interacting chitinase-like protein). A DDSLL motif in the cytoplasmic tail of stabilin-1 interacts with GGA adaptors; however, the deletion of DDSLL reduces but does not abrogate this interaction. Here, we identified a novel GGA-binding site, EDDADDD, in the cytoplasmic tail of stabilin-1. The deletion of EDDADDD impaired and the deletion of both the DDSLL and EDDADDD sites abrogated the interaction of stabilin-1 with GGAs. The surface exposure of stabilin-1 and stabilin-1-mediated endocytosis of acLDL, SPARC, and PL were not affected by the deletion either of DDSLL or EDDADDD or both. At the same time, both GGA-binding sites were necessary for the intracellular sorting of SI-CLP performed by stabilin-1. Our data indicate that the novel GGA-binding site EDDADDD is essential for stabilin-1-mediated intracellular sorting but is not required for endocytosis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter alternatively activated macrophages; mannose 6-phosphate receptors; protein; trafficking; adapters; pathway; cells; identification; endothelium; glut4
ISSN (print) / ISBN 0270-7306
Zeitschrift Molecular and Cellular Biology
Quellenangaben Band: 29, Heft: 22, Seiten: 6097-6105
Verlag American Society for Microbiology (ASM)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)