Autophagy Induction by the Pathogen Receptor CD46

Université de Lyon, Lyon, F-69003, France.
Cell host & microbe (Impact Factor: 12.33). 10/2009; 6(4):354-66. DOI: 10.1016/j.chom.2009.09.006
Source: PubMed


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.

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    • "Rello-Varona et al., 2012; Vitale et al., 2011 ROS non-selective exacerbate DNA damage Bouwman and Jonkers, 2012 senescence nucleophagy CCFs destined to disposal have signs of ongoing DDR and are tagged with p62 Ivanov et al., 2013; Young et al., 2009 Plasma membrane death receptor ligands non-selective stimulate autophagy via JNK1 and components of the NF-kB signaling pathway Criollo et al., 2010; Criollo et al., 2011; He et al., 2012; Keller et al., 2011 GCPR agonists non-selective involves PtdIns(3,4,5)P3 synthesis and increased cAMP levels Wauson et al., 2014 pathogen docking non-selective xenophagy CD46 and CXCR4 promote canonical autophagic responses Espert et al., 2006 Joubert et al., 2009 TLR agonists non-selective xenophagy promote autophagy via MYD88 or TICAM1 Delgado et al., 2008; Knodler and Celli, 2011; Ma et al., 2013; Shi and Kehrl, 2008 amino acid deprivation non-selective several GPCRs repress autophagy in response to extracellular amino acids Wauson et al., 2012; Wauson et al., 2014 DR ligand withdrawal non-selective unknown mechanism Bouhidel et al., 2015; Jimenez-Sanchez et al., 2012 growth factor deprivation RTK inhibitors non-selective promote autophagy by reducing nutrient intake, limiting AKT1 signaling, and derepressing BECN1 Inoki et al., 2002; Leto and Saltiel, 2012; Manning and Cantley, 2007; Wang et al., 2012; Wei et al., 2013 Reticular system disruption of Ca 2+ homeostasis non-selective cytosolic Ca 2+ promotes autophagy via DAPK1, CAMKKb, and PRKCQ Cohen et al., 1997; Høyer-Hansen et al., 2007; Sakaki et al., 2008 ER stress non-selective trigger autophagy via PERK/EIF2a/ATF4, IRE1a/JNK1, and ATF6/DAPK1 signaling B'chir et al., 2013; Gade et al., 2012; Hetz, 2012 unsaturated fatty acids non-selective non-canonical autophagic responses that require an intact GA Niso-Santano et al., 2015 UPR responses to xenobiotic reticulophagy autophagy regulates the ER size when adaptive response are shut off Bolender and Weibel, 1973; Bernales et al., 2006; Schuck et al., 2014 (Continued on next page) "
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