Terje Johansen

Publications (3)18.75 Total impact

• Article: Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC.

  Nicole C McKnight, Harold B J Jefferies, Endalkachew A Alemu, Rebecca E Saunders, Michael Howell, Terje Johansen, Sharon A Tooze
  [show abstract] [hide abstract]
  ABSTRACT: Autophagy is a catabolic process by which cytoplasmic components are sequestered and transported by autophagosomes to lysosomes for degradation, enabling recycling of these components and providing cells with amino acids during starvation. It is a highly regulated process and its deregulation contributes to multiple diseases. Despite its importance in cell homeostasis, autophagy is not fully understood. To find new proteins that modulate starvation-induced autophagy, we performed a genome-wide siRNA screen in a stable human cell line expressing GFP-LC3, the marker-protein for autophagosomes. Using stringent validation criteria, our screen identified nine novel autophagy regulators. Among the hits required for autophagosome formation are SCOC (short coiled-coil protein), a Golgi protein, which interacts with fasciculation and elongation protein zeta 1 (FEZ1), an ULK1-binding protein. SCOC forms a starvation-sensitive trimeric complex with UVRAG (UV radiation resistance associated gene) and FEZ1 and may regulate ULK1 and Beclin 1 complex activities. A second candidate WAC is required for starvation-induced autophagy but also acts as a potential negative regulator of the ubiquitin-proteasome system. The identification of these novel regulatory proteins with diverse functions in autophagy contributes towards a fuller understanding of autophagosome formation.
  The EMBO Journal 02/2012; 31(8):1931-46. · 9.20 Impact Factor
• Article: p62 and NDP52 Proteins Target Intracytosolic Shigella and Listeria to Different Autophagy Pathways

  Serge Mostowy, Vanessa Sancho-Shimizu, Mélanie Anne Hamon, Roxane Simeone, Roland Brosch, Terje Johansen, Pascale Cossart
  [show abstract] [hide abstract]
  ABSTRACT: Autophagy is an important mechanism of innate immune defense. We have recently shown that autophagy components are recruited with septins, a new and increasingly characterized cytoskeleton component, to intracytosolic Shigella that have started to polymerize actin. On the other hand, intracytosolic Listeria avoids autophagy recognition by expressing ActA, a bacterial effector required for actin polymerization. Here, we exploit Shigella and Listeria as intracytosolic tools to characterize different pathways of selective autophagy. We show that the ubiquitin-binding adaptor proteins p62 and NDP52 target Shigella to an autophagy pathway dependent upon septin and actin. In contrast, p62 or NDP52 targets the Listeria ActA mutant to an autophagy pathway independent of septin or actin. TNF-α, a host cytokine produced upon bacterial infection, stimulates p62-mediated autophagic activity and restricts the survival of Shigella and the Listeria ActA mutant. These data provide a new molecular framework to understand the emerging complexity of autophagy and its ability to achieve specific clearance of intracytosolic bacteria.
  Journal of Biological Chemistry 07/2011; 286(30):26987-26995. · 4.77 Impact Factor
• Article: p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways.

  Serge Mostowy, Vanessa Sancho-Shimizu, Mélanie Anne Hamon, Roxane Simeone, Roland Brosch, Terje Johansen, Pascale Cossart
  [show abstract] [hide abstract]
  ABSTRACT: Autophagy is an important mechanism of innate immune defense. We have recently shown that autophagy components are recruited with septins, a new and increasingly characterized cytoskeleton component, to intracytosolic Shigella that have started to polymerize actin. On the other hand, intracytosolic Listeria avoids autophagy recognition by expressing ActA, a bacterial effector required for actin polymerization. Here, we exploit Shigella and Listeria as intracytosolic tools to characterize different pathways of selective autophagy. We show that the ubiquitin-binding adaptor proteins p62 and NDP52 target Shigella to an autophagy pathway dependent upon septin and actin. In contrast, p62 or NDP52 targets the Listeria ActA mutant to an autophagy pathway independent of septin or actin. TNF-α, a host cytokine produced upon bacterial infection, stimulates p62-mediated autophagic activity and restricts the survival of Shigella and the Listeria ActA mutant. These data provide a new molecular framework to understand the emerging complexity of autophagy and its ability to achieve specific clearance of intracytosolic bacteria.
  Journal of Biological Chemistry 06/2011; 286(30):26987-95. · 4.77 Impact Factor