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Regulation of the endosomal SNX27-retromer by OTULIN

Author

Listed:
  • Aurelia Stangl

    (Helmholtz Zentrum München)

  • Paul R. Elliott

    (Francis Crick Avenue
    University of Oxford)

  • Adan Pinto-Fernandez

    (University of Oxford)

  • Sarah Bonham

    (University of Oxford)

  • Luke Harrison

    (German Centre for Diabetes Research (DZD))

  • Annalisa Schaub

    (Helmholtz Zentrum München)

  • Kerstin Kutzner

    (Helmholtz Zentrum München)

  • Kirstin Keusekotten

    (Francis Crick Avenue)

  • Paul T. Pfluger

    (German Centre for Diabetes Research (DZD)
    Technische Universität München)

  • Farid El Oualid

    (UbiQ Bio BV)

  • Benedikt M. Kessler

    (University of Oxford)

  • David Komander

    (Francis Crick Avenue
    The Walter and Eliza Hall Institute of Medical Research)

  • Daniel Krappmann

    (Helmholtz Zentrum München)

Abstract

OTULIN (OTU Deubiquitinase With Linear Linkage Specificity) specifically hydrolyzes methionine1 (Met1)-linked ubiquitin chains conjugated by LUBAC (linear ubiquitin chain assembly complex). Here we report on the mass spectrometric identification of the OTULIN interactor SNX27 (sorting nexin 27), an adaptor of the endosomal retromer complex responsible for protein recycling to the cell surface. The C-terminal PDZ-binding motif (PDZbm) in OTULIN associates with the cargo-binding site in the PDZ domain of SNX27. By solving the structure of the OTU domain in complex with the PDZ domain, we demonstrate that a second interface contributes to the selective, high affinity interaction of OTULIN and SNX27. SNX27 does not affect OTULIN catalytic activity, OTULIN-LUBAC binding or Met1-linked ubiquitin chain homeostasis. However, via association, OTULIN antagonizes SNX27-dependent cargo loading, binding of SNX27 to the VPS26A-retromer subunit and endosome-to-plasma membrane trafficking. Thus, we define an additional, non-catalytic function of OTULIN in the regulation of SNX27-retromer assembly and recycling to the cell surface.

Suggested Citation

  • Aurelia Stangl & Paul R. Elliott & Adan Pinto-Fernandez & Sarah Bonham & Luke Harrison & Annalisa Schaub & Kerstin Kutzner & Kirstin Keusekotten & Paul T. Pfluger & Farid El Oualid & Benedikt M. Kessl, 2019. "Regulation of the endosomal SNX27-retromer by OTULIN," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12309-z
    DOI: 10.1038/s41467-019-12309-z
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    Cited by:

    1. Yesheng Fu & Lei Li & Xin Zhang & Zhikang Deng & Ying Wu & Wenzhe Chen & Yuchen Liu & Shan He & Jian Wang & Yuping Xie & Zhiwei Tu & Yadi Lyu & Yange Wei & Shujie Wang & Chun-Ping Cui & Cui Hua Liu & , 2024. "Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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