Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17

Arasaki, Kohei; Mikami, Yumi; Shames, Stephanie R.; Inoue, Hiroki; Wakana, Yuichi; Tagaya, Mitsuo

doi:10.1038/ncomms15406

Cited by 85 publications

(57 citation statements)

References 47 publications

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“…This siRNA was used in a previous study and shown to specifically knockdown Stx17 [17]. This double knockdown experiment suggests that MAP1B depletion-induced autophagosome accumulation is dependent on Stx17, as seen in normal starvation [9,17,26].…”

Section: Map1b-lc1 Links Stx17 and Mtsmentioning

confidence: 84%

MAP1B‐LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules

et al. 2018

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In fed cells, syntaxin 17 (Stx17) is associated with microtubules at the endoplasmic reticulum-mitochondria interface and promotes mitochondrial fission by determining the localization and function of the mitochondrial fission factor Drp1. Upon starvation, Stx17 dissociates from microtubules and Drp1, and binds to Atg14L, a subunit of the phosphatidylinositol 3-kinase complex, to facilitate phosphatidylinositol 3-phosphate production and thereby autophagosome formation, but the mechanism underlying this phenomenon remains unknown. Here we identify MAP1B-LC1 (microtubule-associated protein 1B-light chain 1) as a critical regulator of Stx17 function. Depletion of MAP1B-LC1 causes Stx17-dependent autophagosome accumulation even under nutrient-rich conditions, whereas its overexpression blocks starvation-induced autophagosome formation. MAP1B-LC1 links microtubules and Stx17 in fed cells, and starvation causes the dephosphorylation of MAP1B-LC1 at Thr217, allowing Stx17 to dissociate from MAP1B-LC1 and bind to Atg14L. Our results reveal the mechanism by which Stx17 changes its binding partners in response to nutrient status.

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Section: Map1b-lc1 Links Stx17 and Mtsmentioning

confidence: 84%

MAP1B‐LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules

et al. 2018

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“…A well-characterized example is Legionella pneumophila , which possesses the effector RavZ to catalyze the irreversible uncoupling of Atg8-family proteins from phosphatidylethnolamine on autophagosonal membranes, allowing L. pneumophila to inhibit autophagy [36,37]. Additionally, the effector Lpg1137 has recently been reported to proteolytically cleave STX17, a protein involved in the fusion of autophagosomes with the lysosome, and a further effector LpSpI, inhibits autophagy through its ability to target host sphingosine biosynthesis [38,39]. In contrast, rather than being bactericidal, the lysosome provides the appropriate environment to induce metabolic activity of Coxiella and promote intracellular replication [8].…”

Section: Discussionmentioning

confidence: 99%

Interaction between autophagic vesicles and the Coxiella-containing vacuole requires CLTC (clathrin heavy chain)

Latomanski

Newton

2018

Autophagy

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Coxiella burnetii is an intracellular bacterial pathogen which causes Q fever, a human infection with the ability to cause chronic disease with potentially life-threatening outcomes. In humans, Coxiella infects alveolar macrophages where it replicates to high numbers in a unique, pathogen-directed lysosome-derived vacuole. This compartment, termed the Coxiella-containing vacuole (CCV), has a low internal pH and contains markers both of lysosomes and autophagosomes. The CCV membrane is also enriched with CLTC (clathrin heavy chain) and this contributes to the success of the CCV. Here, we describe a role for CLTC, a scaffolding protein of clathrin-coated vesicles, in facilitating the fusion of autophagosomes with the CCV. During gene silencing of CLTC, CCVs are unable to fuse with each other, a phenotype also seen when silencing genes involved in macroautophagy/autophagy. MAP1LC3B/LC3B, which is normally observed inside the CCV, is excluded from CCVs in the absence of CLTC. Additionally, this study demonstrates that autophagosome fusion contributes to CCV size as cell starvation and subsequent autophagy induction leads to further CCV expansion. This is CLTC dependent, as the absence of CLTC renders autophagosomes no longer able to contribute to the expansion of the CCV. This investigation provides a functional link between CLTC and autophagy in the context of Coxiella infection and highlights the CCV as an important tool to explore the interactions between these vesicular trafficking pathways.

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“…Highly mobile and dynamic in living cells, mitochondria are the energy‐generating organelles of cells, the disorder of which is associated with various diseases, including Alzheimer's, Parkinson's, and cancer . Recently developed super‐resolution fluorescence microscopies such as stimulated emission deletion (STED), structured illumination microscopy (SIM), and stochastic optical reconstruction microscopy (STORM), as well as other single‐molecule super‐resolution imaging techniques, are enhanced new tools for investigating the dynamics of subcellular structures, including mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Super‐Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

Chen

Jin

Shao

et al. 2018

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100

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Combining luminescent transition metal complex with super‐resolution microscopy is an excellent strategy for the long‐term visualization of the dynamics of subcellular structures in living cells. However, it remains unclear whether iridium(III) complexes are applicable for a particular type of super‐resolution technique, structured illumination microscopy (SIM), to image subcellular structures. Herein, an iridium(III) dye, to track mitochondrial dynamics in living cells under SIM is described. The dye demonstrates excellent specificity and photostability and satisfactory cell permeability. While using SIM to image mitochondria, an ≈80 nm resolution is achieved that allows the clear observation of the structure of mitochondrial cristae. The dye is used to monitor and quantify mitochondrial dynamics relative to lysosomes, including fusion involved in mitophagy, and newly discovered mitochondria–lysosome contact (MLC) under different conditions. The MLC remains intact and fusion vanishes when five receptors, p62, NDP52, OPTN, NBR1, and TAX1BP1, are knocked out, suggesting that these two processes are independent.

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Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17

Cited by 85 publications

References 47 publications

MAP1B‐LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules

MAP1B‐LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules

Interaction between autophagic vesicles and the Coxiella-containing vacuole requires CLTC (clathrin heavy chain)

Super‐Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

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