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Zhang, J.* ; Gratchev, A.* ; Riabov, V.* ; Mamidi, S. ; Schmuttermaier, C.* ; Krusell, L.* ; Kremmer, E. ; Workman, G.* ; Sage, E.H.* ; Jalkanen, S.* ; Goerdt, S.* ; Kzhyshkowska, J.*

A novel GGA-binding site is required for intracellular sorting mediated by stabilin-1.

Mol. Cell. Biol. 29, 6097-6105 (2009)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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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