Mechanism of cargo recognition by retromer-linked SNX-BAR proteins

PLoS Biology
Xin YongDa Jia

Abstract

Endocytic recycling of internalized transmembrane proteins is essential for many important physiological processes. Recent studies have revealed that retromer-related Sorting Nexin family (SNX)-Bin/Amphiphysin/Rvs (BAR) proteins can directly recognize cargoes like cation-independent mannose 6-phosphate receptor (CI-MPR) and Insulin-like growth factor 1 receptor (IGF1R); however, it remains poorly understood how SNX-BARs select specific cargo proteins and whether they recognize additional ligands. Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes. Using this motif, we identified over 70 putative SNX-BAR ligands, many of which play critical roles in apoptosis, cell adhesion, signal transduction, or metabolite homeostasis. Remarkably, SNX-BARs could cooperate with both SNX27 and retromer in the recycling of ligands encompassing the SBM, PDZ-binding motif, or both motifs. Overall, our studies establish that SNX-BARs function as a direct cargo-selecting module for a large set of transmembrane proteins transiting the endosome, in addition to their roles in phospholipid recognit...Continue Reading

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Citations

Dec 17, 2020·American Journal of Physiology. Cell Physiology·Fiona J McDonald
Dec 31, 2020·Cells·Sara E Hanley, Katrina F Cooper
Jan 22, 2021·Cell Death and Differentiation·Julian M CarosiTimothy J Sargeant
Feb 3, 2021·Trends in Biochemical Sciences·Matthew N J Seaman
Mar 4, 2021·International Journal of Molecular Sciences·Bibhas AmatyaPedro A Jose
Mar 23, 2021·Frontiers in Cell and Developmental Biology·Xin YongDa Jia
Apr 2, 2021·Signal Transduction and Targeted Therapy·Xin YongDa Jia
May 4, 2021·Frontiers in Cell and Developmental Biology·Mintu ChandraLauren P Jackson
May 22, 2021·The Journal of Cell Biology·Rylie B WalshAvital A Rodal
Jul 6, 2021·Frontiers in Cell and Developmental Biology·Yingfeng Tu, Matthew N J Seaman
Sep 1, 2021·Proceedings of the National Academy of Sciences of the United States of America·Xin YongDa Jia
Sep 17, 2021·Essays in Biochemistry·Zhe YangRohan D Teasdale

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Methods Mentioned

BETA
pull-down
Isothermal titration calorimetry
NMR
nuclear magnetic resonance
pull down
fluorescence-activated cell sorting
flow cytometry
size-exclusion chromatography
dynamic light scattering
transfection

Software Mentioned

NIH ImageJ
machaccino
ClustalW
Prism
OriginLab
Jpred4
InterPro
HHpred
NMRPipe
Origin

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