Emerging Role of Retromer in Modulating Pathogen Growth

Overview

Journal Trends Microbiol

Date 2018 Apr 29

PMID 29703496

Citations 17

Authors

Cherilyn Elwell

Joanne Engel

Affiliations

Soon will be listed here.

Abstract

Intracellular pathogens have developed elegant mechanisms to modulate host endosomal trafficking. The highly conserved retromer pathway has emerged as an important target of viruses and intravacuolar bacteria. Some pathogens require retromer function to survive. For others, retromer activity restricts intracellular growth; these pathogens must disrupt retromer function to survive. In this review, we discuss recent paradigm changes to the current model for retromer assembly and cargo selection. We highlight how the study of pathogen effectors has contributed to these fundamental insights, with a special focus on the biology and structure of two recently described bacterial effectors, Chlamydia trachomatis IncE and Legionella pneumophila RidL. These two pathogens employ distinct strategies to target retromer components and overcome restriction of intracellular growth imposed by retromer.

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References

Jimenez-Orgaz A, Kvainickas A, Nagele H, Denner J, Eimer S, Dengjel J . Control of RAB7 activity and localization through the retromer-TBC1D5 complex enables RAB7-dependent mitophagy. EMBO J. 2017; 37(2):235-254. PMC: 5770787. DOI: 10.15252/embj.201797128. View

Rzomp K, Scholtes L, Briggs B, Whittaker G, Scidmore M . Rab GTPases are recruited to chlamydial inclusions in both a species-dependent and species-independent manner. Infect Immun. 2003; 71(10):5855-70. PMC: 201052. DOI: 10.1128/IAI.71.10.5855-5870.2003. View

Elwell C, Czudnochowski N, Von Dollen J, Johnson J, Nakagawa R, Mirrashidi K . interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction. Elife. 2017; 6. PMC: 5364026. DOI: 10.7554/eLife.22709. View

Orsel J, Sincock P, Krise J, Pfeffer S . Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein. Proc Natl Acad Sci U S A. 2000; 97(16):9047-51. PMC: 16819. DOI: 10.1073/pnas.160251397. View

Ghai R, Mobli M, Norwood S, Bugarcic A, Teasdale R, King G . Phox homology band 4.1/ezrin/radixin/moesin-like proteins function as molecular scaffolds that interact with cargo receptors and Ras GTPases. Proc Natl Acad Sci U S A. 2011; 108(19):7763-8. PMC: 3093529. DOI: 10.1073/pnas.1017110108. View

Marquer C, Tian H, Yi J, Bastien J, DallArmi C, Yang-Klingler Y . Arf6 controls retromer traffic and intracellular cholesterol distribution via a phosphoinositide-based mechanism. Nat Commun. 2016; 7:11919. PMC: 4931008. DOI: 10.1038/ncomms11919. View

Rudel T, Meyer T . Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells. Cell Microbiol. 2001; 1(3):237-47. DOI: 10.1046/j.1462-5822.1999.00024.x. View

Seaman M, McCaffery J, Emr S . A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast. J Cell Biol. 1998; 142(3):665-81. PMC: 2148169. DOI: 10.1083/jcb.142.3.665. View

Bhowmick S, Chakravarty C, Sellathamby S, Lal S . The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation. Arch Virol. 2016; 162(4):919-929. DOI: 10.1007/s00705-016-3153-8. View

10.

Seaman M, Gautreau A, Billadeau D . Retromer-mediated endosomal protein sorting: all WASHed up!. Trends Cell Biol. 2013; 23(11):522-8. PMC: 3924425. DOI: 10.1016/j.tcb.2013.04.010. View

11.

Finsel I, Hilbi H . Formation of a pathogen vacuole according to Legionella pneumophila: how to kill one bird with many stones. Cell Microbiol. 2015; 17(7):935-50. DOI: 10.1111/cmi.12450. View

12.

Chamberland J, Ritter B . Retromer revisited: Evolving roles for retromer in endosomal sorting. J Cell Biol. 2017; 216(11):3433-3436. PMC: 5674901. DOI: 10.1083/jcb.201708111. View

13.

Moore E, Ouellette S . Reconceptualizing the chlamydial inclusion as a pathogen-specified parasitic organelle: an expanded role for Inc proteins. Front Cell Infect Microbiol. 2014; 4:157. PMC: 4215707. DOI: 10.3389/fcimb.2014.00157. View

14.

Gambarte Tudela J, Capmany A, Romao M, Quintero C, Miserey-Lenkei S, Raposo G . The late endocytic Rab39a GTPase regulates the interaction between multivesicular bodies and chlamydial inclusions. J Cell Sci. 2015; 128(16):3068-81. DOI: 10.1242/jcs.170092. View

15.

Hesketh G, Perez-Dorado I, Jackson L, Wartosch L, Schafer I, Gray S . VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface. Dev Cell. 2014; 29(5):591-606. PMC: 4059916. DOI: 10.1016/j.devcel.2014.04.010. View

16.

Newton H, Ang D, van Driel I, Hartland E . Molecular pathogenesis of infections caused by Legionella pneumophila. Clin Microbiol Rev. 2010; 23(2):274-98. PMC: 2863363. DOI: 10.1128/CMR.00052-09. View

17.

Paul B, Kim H, Kerr M, Huston W, Teasdale R, Collins B . Structural basis for the hijacking of endosomal sorting nexin proteins by . Elife. 2017; 6. PMC: 5348129. DOI: 10.7554/eLife.22311. View

18.

Temkin P, Lauffer B, Jager S, Cimermancic P, Krogan N, Von Zastrow M . SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nat Cell Biol. 2011; 13(6):715-21. PMC: 3113693. DOI: 10.1038/ncb2252. View

19.

Burd C, Cullen P . Retromer: a master conductor of endosome sorting. Cold Spring Harb Perspect Biol. 2014; 6(2). PMC: 3941235. DOI: 10.1101/cshperspect.a016774. View

20.

Popoff V, Mardones G, Tenza D, Rojas R, Lamaze C, Bonifacino J . The retromer complex and clathrin define an early endosomal retrograde exit site. J Cell Sci. 2007; 120(Pt 12):2022-31. DOI: 10.1242/jcs.003020. View