Talk:2010 Lecture 6
- The antiviral signaling protein MAVS is located on both peroxisomes and mitochondria
- RNA viruses activate MAVS-dependent signaling from peroxisomes
- Peroxisomal signaling induces antiviral gene expression but not interferon production
- MAVS signaling from peroxisomes is sufficient to restrict viral replication
- "Peroxisomes have long been established to play a central role in regulating various metabolic activities in mammalian cells. These organelles act in concert with mitochondria to control the metabolism of lipids and reactive oxygen species. However, while mitochondria have emerged as an important site of antiviral signal transduction, a role for peroxisomes in immune defense is unknown. Here, we report that the RIG-I-like receptor (RLR) adaptor protein MAVS is located on peroxisomes and mitochondria. We find that peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. The interferon regulatory factor IRF1 plays a crucial role in regulating MAVS-dependent signaling from peroxisomes. These results establish that peroxisomes are an important site of antiviral signal transduction."
- From the Archive - How to make a lysosome
- Peroxisome biogenesis: the peroxisomal endomembrane system and the role of the ER
- The peroxisome: orchestrating important developmental decisions from inside the cell
- Endosome to trans-Golgi traffic is vesicular Coexpression of fluorescent Rab9 and Rab7 by Barbero et al. revealed that these two late endosome Rabs occupy distinct domains within late endosome membranes. Rab9 is present on endosomes that display bidirectional microtubule-dependent motility, and Rab9-positive transport vesicles (rather than tubules) can be seen moving along microtubule tracks and fusing with the trans-Golgi network.
- Recycling of endosomes by Arf6 Activation of nucleotide exchange on Arf6 causes an increase in both membrane internalization and the return of the resultant structures to the plasma membrane. However, when Brown et al. block Arf6 in its GTP-loaded ("on") state, this results in accumulation of endosome-derived vacuoles.
- Actin tails form behind motile endosomes and lysosomes Taunton et al. document the formation of actin comet tails (red) behind motile endosomes and lysosomes. The tails may help the organelles move around the cell, and influence the construction of the cytoskeleton.
- Lysosomes repair the plasma membrane When cells are injured, calcium rushes in and prompts exocytosis of membranes to repair the gap. Jaiswal et al. confirm that the repairing membranes are from lysosomes.
- Vam6p clusters and fuses lysosomes Caplan et al. find that human Vam6p promotes clustering and then fusion of lysosomes.
- Journal of Cell Biology (JCB) copyright notice extract "Beginning six months after publication, Rockefeller University Press grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode."
- clathrin-independent endocytic pathways
- Autophagy is activated for cell survival after endoplasmic reticulum stress. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K. Mol Cell Biol. 2006 Dec;26(24):9220-31. Epub 2006 Oct 9. PMID: 17030611
- "Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. Treatment of SK-N-SH neuroblastoma cells with ER stressors markedly induced the formation of autophagosomes, which were recognized at the ultrastructural level. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"), representing autophagosomes, was extensively induced in cells exposed to ER stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. Disturbance of autophagy rendered cells vulnerable to ER stress, suggesting that autophagy plays important roles in cell survival after ER stress."
- Abcam - Receptor-mediated endocytosis by clathrin-coated vesicles
- Virus can enter the cell by receptor-mediated endocytosis. Acidification of the endocome, breaks dow the virus capsid.
- For example: adenovirus virions bind to the coxsackie adenovirus receptor (CAR) and integrins on the plasma membrane.