Lysosome-Mediated Plasma Membrane Repair Is Dependent on the Small GTPase Arl8b and Determines Cell Death Type in <i>Mycobacterium tuberculosis</i> Infection

Michelet, Xavier; Tuli, Amit; Gan, Huixian; Geadas, Carolina; Sharma, Mahak; Remold, Heinz G.; Brenner, Michael B.

doi:10.4049/jimmunol.1700829

Cited by 29 publications

(30 citation statements)

References 54 publications

(90 reference statements)

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“…Arl8b facilitates anterograde lysosomal trafficking in response to hepatocyte growth factor, epidermal growth factor, or an acidic extracellular pH, which were shown to be correlated with invasive growth and proteolytic ECM degradation in a 3D model of prostate cancer 52 . Bacterial infection was also shown to activate Arl8b and induce lysosome-mediated plasma membrane repair in HeLa cells and primary macrophages 53 . In addition, the activation of Arl8b by phorbol esters promotes lysosome tubulation in macrophages 54 .…”

Section: Discussionmentioning

confidence: 99%

Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation

Onodera

Giaccia

et al. 2020

Commun Biol

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Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression of ARL8B and BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis.

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Section: Discussionmentioning

confidence: 99%

Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation

Onodera

Giaccia

et al. 2020

Commun Biol

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“…) and Arl8b (Michelet et al . ). The exact mechanism by which lysosomal exocytosis promotes PM repair is still not clearly understood.…”

Section: Sphingolipids and Lysosomal Storage Disorders (Lsds)mentioning

confidence: 97%

Sphingolipids and neuronal degeneration in lysosomal storage disorders

Grassi

Chiricozzi

Mauri

et al. 2018

Journal of Neurochemistry

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Ceramide, sphingomyelin, and glycosphingolipids (both neutral and acidic) are characterized by the presence in the lipid moiety of an aliphatic base known as sphingosine. Altogether, they are called sphingolipids and are particularly abundant in neuronal plasma membranes, where, via interactions with the other membrane lipids and membrane proteins, they play a specific role in modulating the cell signaling processes. The metabolic pathways determining the plasma membrane sphingolipid composition are thus the key point for functional changes of the cell properties. Unnatural changes of the neuronal properties are observed in sphingolipidoses, lysosomal storage diseases occurring when a lysosomal sphingolipid hydrolase is not working, leading to the accumulation of the substrate and to its distribution to all the cell membranes interacting with lysosomes. Moreover, secondary accumulation of sphingolipids is a common trait of other lysosomal storage diseases. Keywords: gangliosides, lysosome, membrane fusion, sphingolipidoses, sphingolipids, sphingomyelin.This article is part of the Special Issue "Lysosomal Storage Disorders".Sphingolipids are amphiphilic membrane lipids characterized by the presence of sphingosine, an amino-and-hydroxy alkylic long chain. After more than a century of studies, we now know their structure, their physico-chemical properties, their distribution and content in cells and tissues of many animal species, including humans . The final cellular site for sphingolipids is the plasma membrane, however, their complex metabolic pathway requires many intracellular processes, so that a not negligible portion of them is also found intracellularly (Sandhoff and Kolter 2003;Schulze et al. 2009;Kolter and Sandhoff 2010;Hannun and Obeid 2018). As amphiphilic compounds they contain a hydrophilic head group, for example a saccharide, an oligosaccharide, a phosphocholine, protruding into the cell aqueous environment, and a hydrophobic chain called ceramide, in which the sphingosine is linked with a fatty acid via an amidic bond, inserted into the outer layer of plasma membrane.Sphingolipids are typically asymmetric components of the plasma membranes enriched in the outer leaflet (van Meer and Hoetzl 2010;van Meer 2011;Fujimoto and Parmryd 2016), however, it cannot be excluded that a minor pool of them could be transiently inserted into the inner layer with the hydrophilic group facing the cytosol. The hydrophilic group, thanks to the presence of carbohydrates and/or ionic charges, attracts water and ions, forms hydrogen bonds and easily interacts with the group of membrane components protruding from the membrane itself. At the water-lipid interface, the sphingolipid ceramide amide linkage accepts hydrogen bonds on the carbonyl group and donates hydrogen bonds via the N-H group, allowing the formation of a double linkage, which works as a padlock within molecules (Fig. 1). The lipid moiety inserted into the lipid layer interacts with the lipid portion of the cholesterol in the membrane and with dip...

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“…We then investigated the role of Arl8b, as a small Ras-like GTPase that localizes exclusively to lysosomes (Xu et al, 2014;Khatter et al, 2015;Michelet et al, 2015;Michelet et al, 2018;Boda et al, 2019) and regulates lysosome movement to the plasma membrane and exocytosis (Michelet et al, 2015). We treated cells with small interfering RNAs (siRNA) targeting Arl8b and obtained ~50% down regulation of Arl8b in cells (Figures S3A and S3B).…”

Section: B-coronaviruses Exit Cells Independently Of the Biosyntheticmentioning

confidence: 99%

β-Coronaviruses use lysosomal organelles for cellular egress

Altan‐Bonnet

Ghosh

et al. 2020

Preprint

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Abstractβ-Coronaviruses are a family of positive-strand enveloped RNA viruses that include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). While much is known regarding their cellular entry and replication pathways, their mode of egress remains uncertain; however, this is assumed to be via the biosynthetic secretory pathway by analogy to other enveloped viruses. Using imaging methodologies in combination with virus-specific reporters, we demonstrate that β-Coronaviruses utilize lysosomal trafficking for egress from cells. This pathway is regulated by the Arf-like small GTPase Arl8b; thus, virus egress is insensitive to inhibitors of the biosynthetic secretory pathway. Coronavirus infection results in lysosome deacidification, inactivation of lysosomal degradation and disruption of antigen presentation pathways. This coronavirus-induced exploitation of lysosomes provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.

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Lysosome-Mediated Plasma Membrane Repair Is Dependent on the Small GTPase Arl8b and Determines Cell Death Type in Mycobacterium tuberculosis Infection

Cited by 29 publications

References 54 publications

Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation

Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation

Sphingolipids and neuronal degeneration in lysosomal storage disorders

β-Coronaviruses use lysosomal organelles for cellular egress

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