Polarized traffic of LRP1 involves AP1B and SNX17 operating on Y-dependent sorting motifs in different pathways

Maribel Donoso, Jorge Cancino, Jiyeon Lee, Peter Van Kerkhof, Claudio Retamal, Guojun D Bu, Alfonso Gonzalez, Alfredo Caceres, Maria Paz Marzolo

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic recycling receptor with two cytoplasmic tyrosine-based basolateral sorting signals. Here we show that during biosynthetic trafficking LRP1 uses AP1B adaptor complex to move from a post-TGN recycling endosome (RE) to the basolateral membrane. Then it recycles basolaterally from the basolateral sorting endosome (BSE) involving recognition by sorting nexin 17 (SNX17). In the biosynthetic pathway, Y 29 but not N 26 from a proximal NPXY directs LRP1 basolateral sorting from the TGN. A N 26A mutant revealed that this NPXY motif recognized by SNX17 is required for the receptor's exit from BSE. An endocytic Y 63ATL 66 motif also functions in basolateral recycling, in concert with an additional endocytic motif (LL 86,87), by preventing LRP1 entry into the transcytotic apical pathway. All this sorting information operates similarly in hippocampal neurons to mediate LRP1 somatodendritic distribution regardless of the absence of AP1B in neurons. LRP1 basolateral distribution results then from spatially and temporally segregation steps mediated by recognition of distinct tyrosine-based motifs. We also demonstrate a novel function of SNX17 in basolateral/ somatodendritic recycling from a different compartment than AP1B endosomes.

Original languageEnglish (US)
Pages (from-to)481-497
Number of pages17
JournalMolecular Biology of the Cell
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Donoso, M., Cancino, J., Lee, J., Van Kerkhof, P., Retamal, C., Bu, G. D., Gonzalez, A., Caceres, A., & Marzolo, M. P. (2009). Polarized traffic of LRP1 involves AP1B and SNX17 operating on Y-dependent sorting motifs in different pathways. Molecular Biology of the Cell, 20(1), 481-497. https://doi.org/10.1091/mbc.E08-08-0805