Autophagy induction by the pathogen receptor CD46.
Autophagy is a highly regulated self-degradative mechanism required at a basal level for intracellular clearance and recycling of cytoplasmic contents. Upon intracellular pathogen invasion, autophagy can be induced as an innate immune mechanism to control infection. Nevertheless, pathogens have developed strategies to avoid or hijack autophagy for their own benefit. The molecular pathways inducing autophagy in response to infection remain poorly documented. We report here that the engagement of CD46, a ubiquitous human surface receptor able to bind several different pathogens, is sufficient to induce autophagy. CD46-Cyt-1, one of the two C-terminal splice variants of CD46, is linked to the autophagosome formation complex VPS34/Beclin1 via its interaction with the scaffold protein GOPC. Measles virus and group A Streptococcus, two CD46-binding pathogens, induce autophagy through a CD46-Cyt-1/GOPC pathway. Thus, upon microorganism recognition, a cell surface pathogen receptor can directly trigger autophagy, a critical step to control infection.
Joubert
Pierre-Emmanuel
PE
Université de Lyon, Lyon, F-69003, France.
Meiffren
Grégory
G
Grégoire
Isabel Pombo
IP
Pontini
Guillemette
G
Richetta
Clémence
C
Flacher
Monique
M
Azocar
Olga
O
Vidalain
Pierre-Olivier
PO
Vidal
Marc
M
Lotteau
Vincent
V
Codogno
Patrice
P
Rabourdin-Combe
Chantal
C
Faure
Mathias
M
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D002352:Carrier Proteins / Q000378:metabolism; D000077614:Golgi Matrix Proteins; D006801:Humans; D008459:Measles virus / Q000276:immunology*; D051916:Membrane Cofactor Protein / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D013297:Streptococcus pyogenes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D002352:Carrier Proteins; D000077614:Golgi Matrix Proteins; D051916:Membrane Cofactor Protein; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D019869:Phosphatidylinositol 3-Kinases; C491997:BECN1 protein, human; C497857:CD46 protein, human; C434484:GOPC protein, human