A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex

T. Clairfeuille, C. Mas, Audrey Chan, Z. Yang, M. Tello-Lafoz, M. Chandra, J. Widagdo, M.C. Kerr, B. Paul, I. Mérida, R.D. Teasdale, Nathan Pavlos, V. Anggono, B.M. Collins

    Research output: Contribution to journalArticle

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    Abstract

    © 2016 Nature America, Inc. All rights reserved.Recycling of internalized receptors from endosomal compartments is essential for the receptors' cell-surface homeostasis. Sorting nexin 27 (SNX27) cooperates with the retromer complex in the recycling of proteins containing type I PSD95-Dlg-ZO1 (PDZ)-binding motifs. Here we define specific acidic amino acid sequences upstream of the PDZ-binding motif required for high-affinity engagement of the human SNX27 PDZ domain. However, a subset of SNX27 ligands, such as the ß 2 adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor, lack these sequence determinants. Instead, we identified conserved sites of phosphorylation that substitute for acidic residues and dramatically enhance SNX27 interactions. This newly identified mechanism suggests a likely regulatory switch for PDZ interaction and protein transport by the SNX27-retromer complex. Defining this SNX27 binding code allowed us to classify more than 400 potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.
    Original languageEnglish
    Pages (from-to)921-932
    JournalNature Structural and Molecular Biology
    Volume23
    Issue number10
    Early online date5 Sep 2016
    DOIs
    Publication statusPublished - Oct 2016

    Fingerprint

    Sorting Nexins
    Recycling
    Protein Transport
    Ligands
    Acidic Amino Acids
    Neuronal Plasticity
    Cell Surface Receptors
    N-Methyl-D-Aspartate Receptors
    Adrenergic Receptors
    Amino Acid Sequence
    Signal Transduction
    Homeostasis
    Phosphorylation

    Cite this

    Clairfeuille, T., Mas, C., Chan, A., Yang, Z., Tello-Lafoz, M., Chandra, M., ... Collins, B. M. (2016). A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Nature Structural and Molecular Biology, 23(10), 921-932. https://doi.org/10.1038/nsmb.3290
    Clairfeuille, T. ; Mas, C. ; Chan, Audrey ; Yang, Z. ; Tello-Lafoz, M. ; Chandra, M. ; Widagdo, J. ; Kerr, M.C. ; Paul, B. ; Mérida, I. ; Teasdale, R.D. ; Pavlos, Nathan ; Anggono, V. ; Collins, B.M. / A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. In: Nature Structural and Molecular Biology. 2016 ; Vol. 23, No. 10. pp. 921-932.
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    abstract = "{\circledC} 2016 Nature America, Inc. All rights reserved.Recycling of internalized receptors from endosomal compartments is essential for the receptors' cell-surface homeostasis. Sorting nexin 27 (SNX27) cooperates with the retromer complex in the recycling of proteins containing type I PSD95-Dlg-ZO1 (PDZ)-binding motifs. Here we define specific acidic amino acid sequences upstream of the PDZ-binding motif required for high-affinity engagement of the human SNX27 PDZ domain. However, a subset of SNX27 ligands, such as the {\ss} 2 adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor, lack these sequence determinants. Instead, we identified conserved sites of phosphorylation that substitute for acidic residues and dramatically enhance SNX27 interactions. This newly identified mechanism suggests a likely regulatory switch for PDZ interaction and protein transport by the SNX27-retromer complex. Defining this SNX27 binding code allowed us to classify more than 400 potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.",
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    Clairfeuille, T, Mas, C, Chan, A, Yang, Z, Tello-Lafoz, M, Chandra, M, Widagdo, J, Kerr, MC, Paul, B, Mérida, I, Teasdale, RD, Pavlos, N, Anggono, V & Collins, BM 2016, 'A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex' Nature Structural and Molecular Biology, vol. 23, no. 10, pp. 921-932. https://doi.org/10.1038/nsmb.3290

    A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. / Clairfeuille, T.; Mas, C.; Chan, Audrey; Yang, Z.; Tello-Lafoz, M.; Chandra, M.; Widagdo, J.; Kerr, M.C.; Paul, B.; Mérida, I.; Teasdale, R.D.; Pavlos, Nathan; Anggono, V.; Collins, B.M.

    In: Nature Structural and Molecular Biology, Vol. 23, No. 10, 10.2016, p. 921-932.

    Research output: Contribution to journalArticle

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    T1 - A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex

    AU - Clairfeuille, T.

    AU - Mas, C.

    AU - Chan, Audrey

    AU - Yang, Z.

    AU - Tello-Lafoz, M.

    AU - Chandra, M.

    AU - Widagdo, J.

    AU - Kerr, M.C.

    AU - Paul, B.

    AU - Mérida, I.

    AU - Teasdale, R.D.

    AU - Pavlos, Nathan

    AU - Anggono, V.

    AU - Collins, B.M.

    PY - 2016/10

    Y1 - 2016/10

    N2 - © 2016 Nature America, Inc. All rights reserved.Recycling of internalized receptors from endosomal compartments is essential for the receptors' cell-surface homeostasis. Sorting nexin 27 (SNX27) cooperates with the retromer complex in the recycling of proteins containing type I PSD95-Dlg-ZO1 (PDZ)-binding motifs. Here we define specific acidic amino acid sequences upstream of the PDZ-binding motif required for high-affinity engagement of the human SNX27 PDZ domain. However, a subset of SNX27 ligands, such as the ß 2 adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor, lack these sequence determinants. Instead, we identified conserved sites of phosphorylation that substitute for acidic residues and dramatically enhance SNX27 interactions. This newly identified mechanism suggests a likely regulatory switch for PDZ interaction and protein transport by the SNX27-retromer complex. Defining this SNX27 binding code allowed us to classify more than 400 potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.

    AB - © 2016 Nature America, Inc. All rights reserved.Recycling of internalized receptors from endosomal compartments is essential for the receptors' cell-surface homeostasis. Sorting nexin 27 (SNX27) cooperates with the retromer complex in the recycling of proteins containing type I PSD95-Dlg-ZO1 (PDZ)-binding motifs. Here we define specific acidic amino acid sequences upstream of the PDZ-binding motif required for high-affinity engagement of the human SNX27 PDZ domain. However, a subset of SNX27 ligands, such as the ß 2 adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor, lack these sequence determinants. Instead, we identified conserved sites of phosphorylation that substitute for acidic residues and dramatically enhance SNX27 interactions. This newly identified mechanism suggests a likely regulatory switch for PDZ interaction and protein transport by the SNX27-retromer complex. Defining this SNX27 binding code allowed us to classify more than 400 potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.

    U2 - 10.1038/nsmb.3290

    DO - 10.1038/nsmb.3290

    M3 - Article

    VL - 23

    SP - 921

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    JO - NATURE STRUCTURAL & MOLECULAR BIOLOGY

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    SN - 1545-9985

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    ER -