1. Necroptosis: (Last) Message in a Bubble
Peter Vandenabeele, Franck Riquet, Benjamin Cappe 
Immunity 
Volume 47, Issue 1, Pages 1-3 (July 2017)
DOI: /j.immuni
Copyright © 2017 Elsevier Inc. Terms and Conditions

2. Figure 1 Additional MLKL Functions Uncovered: Day and Night Jobs
Besides its well-known night job as a molecule disrupting plasma membrane integrity, additional MLKL functions as day jobs are highlighted by Yoon et al. (2017) and Gong et al. (2017). Yoon et al. (2017) have shown MLKL is acting at the homeostatic level on vesicle trafficking. Upon stimulation by TNF or EGF, the receptors TNFR1 or EGFR, respectively, are endocytosed and processed for either degradation or recycling, a process of which MLKL is involved. siRNA silencing or genetic ablation of MLKL delays this process and leads to a prolonged and perturbed signaling. Besides this homeostatic function of MLKL, additional highly inducible functions were discovered in necroptosis. Upon MLKL activation, extracellular vesicles are released from the cell requiring the ESCRT-III system, but there is a difference in the biogenesis of vesicles between Yoon et al. (2017) and Gong et al. (2017) exosomes and ectosomes, respectively. The exosomes derive from the formation of late endosome or multivesicular bodies (MVBs) loaded with intra-luminal vesicles (ILVs). Gong et al. (2017) revealed that MLKL activation causes shedding of permeable phosphatidyl serine-containing vesicles (ectosomes). A rapid calcium influx occurs before membrane permeabilization. In both cases, phosphorylated MLKL is found in the extracellular vesicles (EVs). The ESCRT-III-mediated removal of MLKL allows the cells to produce enhanced levels of cytokines and chemokines, as indicated. Finally, in a ESCRT-III-dependent manner, MLKL is also implicated in the release of vesicles that contain the inflammasome products (e.g., caspase-1, IL-1β).
Immunity  , 1-3DOI: ( /j.immuni )
Copyright © 2017 Elsevier Inc. Terms and Conditions