Open AccessA Novel GGA-Binding Site Is Required for Intracellular Sorting Mediated by Stabilin-1
Author(s) -
Jingjing Zhang,
Alexei Gratchev,
Vladimir Riabov,
Srinivas Mamidi,
Christina Schmuttermaier,
Liis Krusell,
Elisabeth Kremmer,
Gail Workman,
E. Helene Sage,
Sirpa Jalkanen,
Sergij Goerdt,
Julia Kzhyshkowska
Publication year - 2009
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00505-09
Subject(s) - biology , endocytosis , endocytic cycle , microbiology and biotechnology , intracellular , endosome , golgi apparatus , receptor , biochemistry , endoplasmic reticulum
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 (s tabilin-i nteractingc hitinase-l ikep rotein). 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.