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Molecular and Cellular Biology, November 2009, p. 6097-6105, Vol. 29, No. 22
0270-7306/09/$08.00+0     doi:10.1128/MCB.00505-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Novel GGA-Binding Site Is Required for Intracellular Sorting Mediated by Stabilin-1{triangledown}

Jingjing Zhang,1,§ Alexei Gratchev,1,§ Vladimir Riabov,1 Srinivas Mamidi,1,2 Christina Schmuttermaier,1 Liis Krusell,1 Elisabeth Kremmer,2 Gail Workman,3 E. Helene Sage,3 Sirpa Jalkanen,4 Sergij Goerdt,1 and Julia Kzhyshkowska1*

Medical Faculty Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany,1 Helmholtz Center Munich, Munich, Germany,2 Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington,3 MediCity and Department of Medical Microbiology and Immunology, University of Turku and National Public Health Institute, Turku, Finland4

Received 18 April 2009/ Returned for modification 29 May 2009/ Accepted 24 August 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.

* Corresponding author. Mailing address: Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany. Phone: 49 621 383 2440. Fax: 49 621 383 3815. E-mail: julia.kzhyshkowska{at}umm.de

{triangledown} Published ahead of print on 14 September 2009.

§ Jingjing Zhang and Alexei Gratchev contributed equally to this work.

Molecular and Cellular Biology, November 2009, p. 6097-6105, Vol. 29, No. 22
0270-7306/09/$08.00+0     doi:10.1128/MCB.00505-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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