ZFIN ID: ZDB-PUB-141209-12
DRAM1 promotes the targeting of mycobacteria to selective autophagy
Meijer, A.H., van der Vaart, M.
Date: 2014
Source: Autophagy   10(12): 2389-91 (Other)
Registered Authors: Meijer, Annemarie H., van der Vaart, Michiel
Keywords: DRAM1, LC3, MYD88, Mycobacterium marinum, Mycobacterium tuberculosis, NFκB, STING, macrophages, p62, zebrafish
MeSH Terms:
  • Animals
  • Autophagy*
  • Humans
  • Macrophages/microbiology*
  • Membrane Proteins/metabolism*
  • Mycobacterium/pathogenicity*
  • Mycobacterium Infections/metabolism*
  • Myeloid Differentiation Factor 88/metabolism*
PubMed: 25484076 Full text @ Autophagy
Autophagy provides an important defense mechanism against intracellular bacteria, such as Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis disease (TB). We recently reported that pathogen recognition and antibacterial autophagy are connected by the induction of the DNA damage-regulated autophagy modulator DRAM1 via the toll-like receptor (TLR)-MYD88-NFKB innate immunity signaling pathway. Having shown that DRAM1 colocalizes with Mtb in human macrophages, we took advantage of a zebrafish model for TB to investigate the function of DRAM1 in autophagic host defense in vivo. We found that DRAM1 protects the zebrafish host from infection with Mycobacterium marinum (Mm), a close relative of Mtb. Overexpression of DRAM1 increases autophagosome formation and promotes autophagic flux by a mechanism dependent on the cytosolic DNA sensor TMEM173/STING and the ubiquitin receptor SQSTM1/p62. Here we summarize and discuss the implications of these findings.