Recruitment of TBK1 to cytosol‐invading Salmonella induces WIPI2‐dependent antibacterial autophagy
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Mammalian cells deploy autophagy to defend their cytosol against bacterial invaders. Anti-bacterial autophagy relies on the core autophagy machinery, cargo receptors, and "eat-me" signals such as galectin-8 and ubiquitin that label bacteria as autophagy cargo. Anti-bacterial autophagy also requires the kinase TBK1, whose role in autophagy has remained enigmatic. Here we show that recruitment of WIPI2, itself essential for anti-bacterial autophagy, is dependent on the localization of catalytically active TBK1 to the vicinity of cytosolic bacteria. Experimental manipulation of TBK1 recruitment revealed that engagement of TBK1 with any of a variety of Salmonella-associated "eat-me" signals, including host-derived glycans and K48- and K63-linked ubiquitin chains, suffices to restrict bacterial proliferation. Promiscuity in recruiting TBK1 via independent signals may buffer TBK1 functionality from potential bacterial antagonism and thus be of evolutionary advantage to the host.
Date Issued
2016-08-15
Date Acceptance
2016-05-24
Citation
EMBO Journal, 2016, 35 (16), pp.1779-1792
ISSN
0261-4189
Publisher
EMBO Press
Start Page
1779
End Page
1792
Journal / Book Title
EMBO Journal
Volume
35
Issue
16
Copyright Statement
© 2016 MRC Laboratory of Molecular Biology Published under the terms of the CC BY 4.0 license
License URL
Identifier
PII: embj.201694491
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
anti-bacterial autophagy
PI(3) P
Salmonella
TBK1
WIPI
KAPPA-B ACTIVATION
UBIQUITIN CHAINS
RECEPTOR NDP52
PHOSPHATIDYLINOSITOL 3-PHOSPHATE
MOLECULAR-BASIS
RECOGNITION
DOMAIN
LOCALIZATION
PROTEINS
DEFENSE
PI(3)P
Salmonella
TBK1
WIPI
anti‐bacterial autophagy
Animals
Autophagy
Carrier Proteins
Cytosol
Humans
Immunity, Innate
Membrane Proteins
Mice
Phosphate-Binding Proteins
Protein-Serine-Threonine Kinases
Salmonella typhimurium
Cytosol
Animals
Humans
Mice
Salmonella typhimurium
Protein-Serine-Threonine Kinases
Carrier Proteins
Phosphate-Binding Proteins
Membrane Proteins
Autophagy
Immunity, Innate
06 Biological Sciences
08 Information and Computing Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status
Published
Date Publish Online
2016-07-01