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Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA

Nielsen, M. S., Gustafsen, C., Madsen, P., Nyengaard, J. R., Hermey, G., Bakke, O., Mari, M., Schu, P., Pohlmann, R., Dennes, A. & Petersen, C. M., Oct-2007, In : Molecular and Cellular Biology. 27, 19, p. 6842-51 10 p.

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  • Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA

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DOI

  • Morten S Nielsen
  • Camilla Gustafsen
  • Peder Madsen
  • Jens R Nyengaard
  • Guido Hermey
  • Oddmund Bakke
  • Muriel Mari
  • Peter Schu
  • Regina Pohlmann
  • André Dennes
  • Claus M Petersen

SorLA/LR11 (250 kDa) is the largest and most composite member of the Vps10p-domain receptors, a family of type 1 proteins preferentially expressed in neuronal tissue. SorLA binds several ligands, including neurotensin, platelet-derived growth factor-bb, and lipoprotein lipase, and via complex-formation with the amyloid precursor protein it downregulates generation of Alzheimer's disease-associated Abeta-peptide. The receptor is mainly located in vesicles, suggesting a function in protein sorting and transport. Here we examined SorLA's trafficking using full-length and chimeric receptors and find that its cytoplasmic tail mediates efficient Golgi body-endosome transport, as well as AP-2 complex-dependent endocytosis. Functional sorting sites were mapped to an acidic cluster-dileucine-like motif and to a GGA binding site in the C terminus. Experiments in permanently or transiently AP-1 mu1-chain-deficient cells established that the AP-1 adaptor complex is essential to SorLA's transport between Golgi membranes and endosomes. Our results further implicate the GGA proteins in SorLA trafficking and provide evidence that SNX1 and Vps35, as parts of the retromer complex or possibly in a separate context, are engaged in retraction of the receptor from endosomes.

Original languageEnglish
Pages (from-to)6842-51
Number of pages10
JournalMolecular and Cellular Biology
Volume27
Issue number19
Publication statusPublished - Oct-2007
Externally publishedYes

    Keywords

  • Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Amyloid beta-Protein Precursor, Animals, Cell Line, Cricetinae, Cricetulus, Endosomes, Golgi Apparatus, Humans, LDL-Receptor Related Proteins, Membrane Glycoproteins, Membrane Transport Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Protein Structure, Tertiary, Protein Transport, RNA Interference, Receptors, Interleukin-2, Recombinant Fusion Proteins, Two-Hybrid System Techniques, MANNOSE 6-PHOSPHATE RECEPTOR, TRANS-GOLGI NETWORK, FAMILY-MEMBER, MOSAIC RECEPTOR, GENE FAMILY, LR11, RETROMER, ENDOSOMES, PACS-1, ENZYME

ID: 16003678