Association with PAK2 Enables Functional Interactions of Lentiviral Nef Proteins with the Exocyst Complex

MBio
Andrea ImleOliver T Fackler

Abstract

Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication and contributes to immune evasion in vivo, but the underlying molecular mechanisms remain incompletely defined. Nef interferes with host cell actin dynamics to restrict T lymphocyte responses to chemokine stimulation and T cell receptor engagement. This relies on the assembly of a labile multiprotein complex including the host kinase PAK2 that Nef usurps to phosphorylate and inactivate the actin-severing factor cofilin. Components of the exocyst complex (EXOC), an octameric protein complex involved in vesicular transport and actin remodeling, were recently reported to interact with Nef via the same molecular surface that mediates PAK2 association. Exploring the functional relevance of EXOC in Nef-PAK2 complex assembly/function, we found Nef-EXOC interactions to be specifically mediated by the PAK2 interface of Nef, to occur in infected human T lymphocytes, and to be conserved among lentiviral Nef proteins. In turn, EXOC was dispensable for direct downstream effector functions of Nef-associated PAK2. Surprisingly, PAK2 was essential for Nef-EXOC association, which required a functional Rac1/Cdc42 binding site but not the catalytic activity of PAK2. EXOC w...Continue Reading

References

Nov 17, 1995·Science·K K Van RompayM L Marthas
Aug 1, 1995·Journal of Virology·C Aiken, D Trono
Jan 26, 1995·The New England Journal of Medicine·F KirchhoffR C Desrosiers
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·H M CraigJ C Guatelli
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·J A Schrager, J W Marsh
Dec 23, 1999·Current Biology : CB·G H RenkemaK Saksela
Mar 14, 2000·Molecular and Cellular Biology·O T FacklerB M Peterlin
Jul 21, 2001·EMBO Reports·M GeyerB M Peterlin
Dec 12, 2001·Nature Cell Biology·Serge MoskalenkoMichael A White
Dec 18, 2001·Nature Cell Biology·Kazuhiro SugiharaYasutaka Ohta
Sep 7, 2002·Molecular and Cellular Biology·G Herma RenkemaKalle Saksela
Oct 2, 2002·The Journal of Biological Chemistry·Evangeline Y ChoeIn-Woo Park
Oct 4, 2003·The Journal of Biological Chemistry·Serge MoskalenkoMichael A White
Mar 30, 2004·Journal of Virology·Ellen KrautkrämerOliver T Fackler
Jan 18, 2006·Journal of Virology·Eduardo O'NeillJohn L Foster
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Thorsten BaustBernard Hoflack
Nov 7, 2006·Nature Cell Biology·Xiaofeng ZuoWei Guo
Jan 30, 2007·Nature Reviews. Immunology·Daniel D BilladeauTimothy S Gomez
Apr 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Massimo PizzatoHeinrich G Göttlinger
Feb 1, 2008·The Journal of Biological Chemistry·Ting-Chi LuPaul E Klotman
Jun 11, 2008·The Journal of Cell Biology·Mika Sakurai-YagetaPhilippe Chavrier

❮ Previous
Next ❯

Citations

May 6, 2016·Frontiers in Cell and Developmental Biology·Magdalena Martin-UrdirozIsabelle Jourdain
Aug 26, 2016·Virology·Andrea ImleOliver T Fackler
Dec 25, 2015·PloS One·Marta Martínez-BonetRicardo Madrid
Apr 22, 2017·Pathogens·Simona John Von FreyendChristian Doerig
Feb 7, 2018·Viruses·Alberto Ospina Stella, Stuart Turville
Feb 10, 2018·Frontiers in Immunology·Maeva DupontChristel Vérollet
Sep 28, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miguel Lamas-MuruaOliver T Fackler
Feb 7, 2020·Journal of Virology·Robert J J JansensHerman W Favoreel
May 2, 2020·Viruses·Maeva Dupont, Quentin James Sattentau
Jul 5, 2019·Retrovirology·Elodie MaillerJuan S Bonifacino
Nov 5, 2020·The EMBO Journal·Sheetal KawOliver T Fackler

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
immunoprecipitations
coimmunoprecipitation
immunoprecipitation
GTPase
flow cytometry
fluorescence-activated cell sorting
FACS
transfection
FCS

Software Mentioned

EXOC
Quantity One
cellM
Nef
ImageJ
Volocity
GraphPad Prism
Excel

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Advanced Imaging of Cellular Signaling

Cell signaling is a vital mechanism for communication within cells and outside with the environment. Several different signaling pathways have been found and advanced imaging techniques are being developed to visualize the molecules involved in these signaling pathways. Find the latest research in advanced imaging of cellular signaling here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.