Polarized traffic of LRP1 involves AP1B and SNX17 operating on Y-dependent sorting motifs in different pathways.
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(26)A mutant revealed that this NPXY motif recognized by SNX17 is required for the receptor's exit from BSE. An endocytic Y(63)ATL(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.
Donoso
Maribel
M
Centro de Regulación Celular y Patología , Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile and the Millenium Institute for Fundamental and Applied Biology, Santiago, Chile.
Cancino
Jorge
J
Lee
Jiyeon
J
van Kerkhof
Peter
P
Retamal
Claudio
C
Bu
Guojun
G
Gonzalez
Alfonso
A
Cáceres
Alfredo
A
Marzolo
María-Paz
MP
D033961:Adaptor Protein Complex 1 / Q000235:genetics / Q000378:metabolism*; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism
D033961:Adaptor Protein Complex 1; D033966:Adaptor Protein Complex beta Subunits; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D021382:Protein Sorting Signals; D033921:Vesicular Transport Proteins