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Retriever是一种用于非依赖回收体的内体货物循环的多蛋白复合体。

Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling.

作者信息

McNally Kerrie E, Faulkner Rebecca, Steinberg Florian, Gallon Matthew, Ghai Rajesh, Pim David, Langton Paul, Pearson Neil, Danson Chris M, Nägele Heike, Morris Lindsey L, Singla Amika, Overlee Brittany L, Heesom Kate J, Sessions Richard, Banks Lawrence, Collins Brett M, Berger Imre, Billadeau Daniel D, Burstein Ezra, Cullen Peter J

机构信息

School of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.

Department of Internal Medicine and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

出版信息

Nat Cell Biol. 2017 Oct;19(10):1214-1225. doi: 10.1038/ncb3610. Epub 2017 Sep 11.


DOI:10.1038/ncb3610
PMID:28892079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5790113/
Abstract

Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to CCC (CCDC93, CCDC22, COMMD) and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of αβ integrin. Through quantitative proteomic analysis, we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, that require SNX17-retriever to maintain their surface levels. Our identification of retriever establishes a major endosomal retrieval and recycling pathway.

摘要

在被内吞进入内体网络后,整合膜蛋白会进行分选以便进行溶酶体降解,或者被回收并循环回到细胞表面。在这里,我们描述了一种古老且保守的多蛋白复合物的发现,该复合物协调货物回收和循环,并且重要的是,在生化和功能上与已确立的逆转录酶途径不同。我们将这个复合物称为“retriever”;它是一个由DSCR3、C16orf62和VPS29组成的异源三聚体,与逆转录酶有显著相似性。我们确定retriever与货物衔接蛋白分选连接蛋白17(SNX17)结合,并与CCC(CCDC93、CCDC22、COMMD)和WASH复合物耦合,以防止溶酶体降解并促进αβ整合素的细胞表面循环。通过定量蛋白质组学分析,我们鉴定出超过120种细胞表面蛋白,包括许多整合素、信号受体和溶质转运体,它们需要SNX17-retriever来维持其表面水平。我们对retriever的鉴定建立了一条主要的内体回收和循环途径。

相似文献

[1]
Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling.

Nat Cell Biol. 2017-10

[2]
Towards a molecular understanding of endosomal trafficking by Retromer and Retriever.

Traffic. 2019-7

[3]
Structural basis for Retriever-SNX17 assembly and endosomal sorting.

Nat Commun. 2024-11-25

[4]
Sorting nexin 17 (SNX17) links endosomal sorting to Eps15 homology domain protein 1 (EHD1)-mediated fission machinery.

J Biol Chem. 2020-2-10

[5]
Mechanism and regulation of cargo entry into the Commander endosomal recycling pathway.

Nat Commun. 2024-8-21

[6]
Selective cargo and membrane recognition by SNX17 regulates its interaction with Retriever.

EMBO Rep. 2025-1

[7]
A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport.

Nat Cell Biol. 2013-4-7

[8]
Human Papillomavirus 16 L2 Recruits both Retromer and Retriever Complexes during Retrograde Trafficking of the Viral Genome to the Cell Nucleus.

J Virol. 2021-1-13

[9]
Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50.

J Cell Sci. 2017-1-15

[10]
The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics.

J Cell Sci. 2010-10-5

引用本文的文献

[1]
RABGAP1 is a sensor that facilitates the sorting and processing of amyloid precursor protein.

EMBO J. 2025-8-26

[2]
A Commander-independent function of COMMD3 in endosomal trafficking.

Elife. 2025-8-21

[3]
The Rab32-LRMDA-Retriever Complex is a Key Regulator of Intestinal Immune Homeostasis.

bioRxiv. 2025-7-19

[4]
Tau uptake by human neurons depends on receptor LRP1 and kinase LRRK2.

EMBO J. 2025-8-11

[5]
Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation.

Nat Commun. 2025-7-30

[6]
Identification of a VPS29 isoform with restricted association to Retriever and Retromer accessory proteins through autoinhibition.

Proc Natl Acad Sci U S A. 2025-7-8

[7]
CCDC22 mutations that impair COMMD binding cause attenuated 3C/Ritscher-Schinzel syndrome.

BMC Med Genomics. 2025-5-30

[8]
Disruption of Retriever Function Impacts Retrograde Trafficking From Endosomes.

Cell Biol Int. 2025-8

[9]
EndoMAP.v1 charts the structural landscape of human early endosome complexes.

Nature. 2025-5-28

[10]
Phosphorylation of SNX17 impedes activation of Retriever-mediated sorting.

J Biol Chem. 2025-5-9

本文引用的文献

[1]
Structural Mechanism for Cargo Recognition by the Retromer Complex.

Cell. 2016-12-1

[2]
Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization.

J Cell Sci. 2017-1-15

[3]
WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors.

Proc Natl Acad Sci U S A. 2016-10-4

[4]
A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex.

Nat Struct Mol Biol. 2016-9-5

[5]
Atypical parkinsonism-associated retromer mutant alters endosomal sorting of specific cargo proteins.

J Cell Biol. 2016-8-15

[6]
CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL.

Nat Commun. 2016-3-11

[7]
Endocytic membrane trafficking and neurodegenerative disease.

Cell Mol Life Sci. 2016-4

[8]
PANTHER version 10: expanded protein families and functions, and analysis tools.

Nucleic Acids Res. 2016-1-4

[9]
Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling.

J Cell Biol. 2015-11-9

[10]
Retromer and sorting nexins in endosomal sorting.

Biochem Soc Trans. 2015-2

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