The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Nicholas T Ktistakis - One of the best experts on this subject based on the ideXlab platform.
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Dynamic modelling suggests differential mechanisms for initiation of non-selective autophagy and mitophagy
bioRxiv, 2018Co-Authors: Piero Dalle Pezze, Varvara Kandia, Eleftherios Karanasios, Nicholas T Ktistakis, Simon Walker, Nicolas Le NovèreAbstract:In the initiation phase of autophagy, the ULK1 complex translocates to endoplasmic reticulum membranes which eventually give rise to autophagosomes via an Omegasome intermediate. We studied ULK1 complex accumulation in both starvation-induced non-selective autophagy and ivermectin-induced selective autophagy of mitochondria (mitophagy) using fluorescence imaging and mathematical modelling. In non-selective autophagy, a single accumulation event occurred, whose intensity and duration were reduced upon wortmannin-dependent inhibition of the Class III PI-3 kinase VPS34 and a block in Omegasome formation. In contrast, oscillatory dynamics were observed in mitophagy, with increasing time between peaks. We hypothesise that these oscillations reveal successive ULK1 complex translocations, each similar to the event observed in non-selective autophagy. These translocations would only happen on portions of the mitochondrial surface not already covered by LC3-containing autophagosomal membrane. Our mathematical model reproduced ULK1 repeated aggregations (oscillations) and predicted a positive correlation between the number of events and the mitochondrial diameter.
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UNIT 12.34 Imaging Autophagy
Current protocols in cytometry, 2014Co-Authors: Eleftherios Karanasios, Maria Manifava, Eloise Stapleton, Nicholas T KtistakisAbstract:Autophagy is a membrane-trafficking pathway activated to deliver cytosolic material for degradation to lysosomes through a novel membrane compartment, the autophagosome. Fluorescence microscopy is the most common method used to visualize proteins inside cells, and it is widely used in the autophagy field. To distinguish it from the cellular background, the protein of interest (POI) is either fused with a genetically encoded fluorescent protein or stained with an antibody that is conjugated to an inorganic fluorescent compound. Genetic tagging of the POI allows its visualization in live cells, while immunostaining of the POI requires the fixation of cells and the permeabilization of cell membranes. Here we describe detailed protocols on how to visualize autophagy dynamics using fluorescence microscopy in live and fixed cells. We discuss the critical parameters of each technique, their advantages, and why the robustness is increased when they are used in tandem. Curr. Protoc. Cytom. 69:12.34.1-12.34.16. © 2014 by John Wiley & Sons, Inc. Keywords: autophagy; Omegasomes; ULK1; fluorescence microscopy; live-cell imaging
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Characteristics and requirements of basal autophagy in HEK 293 cells.
Autophagy, 2013Co-Authors: Patience Musiwaro, Maria Manifava, Simon Walker, Matthew Smith, Nicholas T KtistakisAbstract:Basal autophagy-here defined as macroautophagic activity during cellular growth in normal medium containing amino acids and serum-appears to be highly active in many cell types and in animal tissues. Here we characterized this pathway in mammalian HEK 293 cells. First, we examined, side by side, three compounds that are widely used to reveal basal autophagy by blocking maturation of autophagosomes: bafilomycin A 1 (BafA1), chloroquine and vinblastine. Only BafA1 appeared to be without complicating side effects. Chloroquine partially inhibited mechanistic target of rapamycin (MTOR) activity, which would induce autophagy induction as well as block autophagosome maturation. Vinblastine caused the distribution of early Omegasome components into punctate phagophore assembly sites, and therefore it would also induce autophagy, complicating interpretation. Basal autophagy was significantly sensitive to inhibition by wortmannin, and therefore required formation of phosphatidylinositol 3-phosphate (PtdIns3P), but it was twice as resistant to wortmannin as starvation-induced autophagy. We also determined that basal autophagy was significantly suppressed by MTOR activation brought about by overexpression of RHEB or activated RAGs. Finally we investigated the spatial relationship of nascent autophagosomes to the endoplasmic reticulum (ER) or to mitochondria by live imaging experiments under conditions that reveal basal autophagy (with BafA1 treatment), or upon MTOR inactivation (which would result in autophagy induction). Side-by-side comparison showed that under both basal and induced autophagy, 100% of autophagosomes first appeared in close proximity to ER strands. In parallel measurements, 40% were in close proximity to mitochondria under both conditions. We concluded that in HEK 293 cells, basal autophagy is mechanistically similar to that induced by MTOR inactivation in all aspects examined.
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Omegasomes: PI3P platforms that manufacture autophagosomes.
Essays in biochemistry, 2013Co-Authors: Rebecca Roberts, Nicholas T KtistakisAbstract:Autophagy is a conserved survival pathway, which cells and tissues will activate during times of stress. It is characterized by the formation of double-membrane vesicles called autophagosomes inside the cytoplasm. The molecular mechanisms and the signalling components involved require specific control to ensure correct activation. The present chapter describes the formation of autophagosomes from within Omegasomes, newly identified membrane compartments enriched in PI3P (phosphatidylinositol 3-phosphate) that serve as platforms for the formation of at least some autophagosomes. We discuss the signalling events required to nucleate the formation of Omegasomes as well as the protein complexes involved.
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Dynamic association of the ULK1 complex with Omegasomes during autophagy induction.
Journal of cell science, 2013Co-Authors: Eleftherios Karanasios, Takeshi Kaizuka, Maria Manifava, Noboru Mizushima, Eloise Stapleton, Simon A Walker, Nicholas T KtistakisAbstract:Induction of autophagy requires the ULK1 protein kinase complex and the Vps34 lipid kinase complex. PtdIns3P synthesised by Vps34 accumulates in Omegasomes, membrane extensions of the ER within which some autophagosomes form. The ULK1 complex is thought to target autophagosomes independently of PtdIns3P, and its functional relationship to Omegasomes is unclear. Here we show that the ULK1 complex colocalises with Omegasomes in a PtdIns3P-dependent way. Live-cell imaging of Atg13 (a ULK1 complex component), Omegasomes and LC3 establishes and annotates for the first time a complete sequence of steps leading to autophagosome formation, as follows. Upon starvation, the ULK1 complex forms puncta associated with the ER and sporadically with mitochondria. If PtdIns3P is available, these puncta become Omegasomes. Subsequently, the ULK1 complex exits Omegasomes and autophagosomes bud off. If PtdIns3P is unavailable, ULK1 puncta are greatly reduced in number and duration. Atg13 contains a region with affinity for acidic phospholipids, required for translocation to punctate structures and autophagy progression.
Takao Hamakubo - One of the best experts on this subject based on the ideXlab platform.
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phosphatidylinositol 3 phosphatase myotubularin related protein 6 mtmr6 is regulated by small gtpase rab1b in the early secretory and autophagic pathways
Journal of Biological Chemistry, 2013Co-Authors: Yasuhiro Mochizuki, Riuko Ohashi, Makoto Naito, Hiroko Iwanari, Tatsuhiko Kodama, Takeshi Kawamura, Takao HamakuboAbstract:Abstract A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular Omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.
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phosphatidylinositol 3 phosphatase myotubularin related protein 6 mtmr6 is regulated by small gtpase rab1b in the early secretory and autophagic pathways
Journal of Biological Chemistry, 2013Co-Authors: Yasuhiro Mochizuki, Riuko Ohashi, Makoto Naito, Hiroko Iwanari, Tatsuhiko Kodama, Takeshi Kawamura, Takao HamakuboAbstract:Abstract A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular Omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.
Yasuhiro Mochizuki - One of the best experts on this subject based on the ideXlab platform.
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phosphatidylinositol 3 phosphatase myotubularin related protein 6 mtmr6 is regulated by small gtpase rab1b in the early secretory and autophagic pathways
Journal of Biological Chemistry, 2013Co-Authors: Yasuhiro Mochizuki, Riuko Ohashi, Makoto Naito, Hiroko Iwanari, Tatsuhiko Kodama, Takeshi Kawamura, Takao HamakuboAbstract:Abstract A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular Omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.
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phosphatidylinositol 3 phosphatase myotubularin related protein 6 mtmr6 is regulated by small gtpase rab1b in the early secretory and autophagic pathways
Journal of Biological Chemistry, 2013Co-Authors: Yasuhiro Mochizuki, Riuko Ohashi, Makoto Naito, Hiroko Iwanari, Tatsuhiko Kodama, Takeshi Kawamura, Takao HamakuboAbstract:Abstract A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular Omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.
Maria Manifava - One of the best experts on this subject based on the ideXlab platform.
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selective autophagy of mitochondria on a ubiquitin endoplasmic reticulum platform
Developmental Cell, 2019Co-Authors: Maria Zachari, Sigurdur Runar Gudmundsson, Ziyue Li, Maria Manifava, James Stronge, Eleftherios Karanasios, Caterina Piunti, Ronak Shah, Matthew Smith, Chieko KishiitakuraAbstract:Summary The dynamics and coordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experiments to address these questions. Ubiquitination of mitochondrial fragments is required the earliest, followed by auto-phosphorylation of TBK1. Next, early essential autophagy proteins FIP200 and ATG13 act at different steps, whereas ULK1 and ULK2 are dispensable. Receptors act temporally and mechanistically upstream of ATG13 but downstream of FIP200. The VPS34 complex functions at the Omegasome step. ATG13 and optineurin target mitochondria in a discontinuous oscillatory way, suggesting multiple initiation events. Targeted ubiquitinated mitochondria are cradled by endoplasmic reticulum (ER) strands even without functional autophagy machinery and mitophagy adaptors. We propose that damaged mitochondria are ubiquitinated and dynamically encased in ER strands, providing platforms for formation of the mitophagosomes.
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UNIT 12.34 Imaging Autophagy
Current protocols in cytometry, 2014Co-Authors: Eleftherios Karanasios, Maria Manifava, Eloise Stapleton, Nicholas T KtistakisAbstract:Autophagy is a membrane-trafficking pathway activated to deliver cytosolic material for degradation to lysosomes through a novel membrane compartment, the autophagosome. Fluorescence microscopy is the most common method used to visualize proteins inside cells, and it is widely used in the autophagy field. To distinguish it from the cellular background, the protein of interest (POI) is either fused with a genetically encoded fluorescent protein or stained with an antibody that is conjugated to an inorganic fluorescent compound. Genetic tagging of the POI allows its visualization in live cells, while immunostaining of the POI requires the fixation of cells and the permeabilization of cell membranes. Here we describe detailed protocols on how to visualize autophagy dynamics using fluorescence microscopy in live and fixed cells. We discuss the critical parameters of each technique, their advantages, and why the robustness is increased when they are used in tandem. Curr. Protoc. Cytom. 69:12.34.1-12.34.16. © 2014 by John Wiley & Sons, Inc. Keywords: autophagy; Omegasomes; ULK1; fluorescence microscopy; live-cell imaging
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Characteristics and requirements of basal autophagy in HEK 293 cells.
Autophagy, 2013Co-Authors: Patience Musiwaro, Maria Manifava, Simon Walker, Matthew Smith, Nicholas T KtistakisAbstract:Basal autophagy-here defined as macroautophagic activity during cellular growth in normal medium containing amino acids and serum-appears to be highly active in many cell types and in animal tissues. Here we characterized this pathway in mammalian HEK 293 cells. First, we examined, side by side, three compounds that are widely used to reveal basal autophagy by blocking maturation of autophagosomes: bafilomycin A 1 (BafA1), chloroquine and vinblastine. Only BafA1 appeared to be without complicating side effects. Chloroquine partially inhibited mechanistic target of rapamycin (MTOR) activity, which would induce autophagy induction as well as block autophagosome maturation. Vinblastine caused the distribution of early Omegasome components into punctate phagophore assembly sites, and therefore it would also induce autophagy, complicating interpretation. Basal autophagy was significantly sensitive to inhibition by wortmannin, and therefore required formation of phosphatidylinositol 3-phosphate (PtdIns3P), but it was twice as resistant to wortmannin as starvation-induced autophagy. We also determined that basal autophagy was significantly suppressed by MTOR activation brought about by overexpression of RHEB or activated RAGs. Finally we investigated the spatial relationship of nascent autophagosomes to the endoplasmic reticulum (ER) or to mitochondria by live imaging experiments under conditions that reveal basal autophagy (with BafA1 treatment), or upon MTOR inactivation (which would result in autophagy induction). Side-by-side comparison showed that under both basal and induced autophagy, 100% of autophagosomes first appeared in close proximity to ER strands. In parallel measurements, 40% were in close proximity to mitochondria under both conditions. We concluded that in HEK 293 cells, basal autophagy is mechanistically similar to that induced by MTOR inactivation in all aspects examined.
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Dynamic association of the ULK1 complex with Omegasomes during autophagy induction.
Journal of cell science, 2013Co-Authors: Eleftherios Karanasios, Takeshi Kaizuka, Maria Manifava, Noboru Mizushima, Eloise Stapleton, Simon A Walker, Nicholas T KtistakisAbstract:Induction of autophagy requires the ULK1 protein kinase complex and the Vps34 lipid kinase complex. PtdIns3P synthesised by Vps34 accumulates in Omegasomes, membrane extensions of the ER within which some autophagosomes form. The ULK1 complex is thought to target autophagosomes independently of PtdIns3P, and its functional relationship to Omegasomes is unclear. Here we show that the ULK1 complex colocalises with Omegasomes in a PtdIns3P-dependent way. Live-cell imaging of Atg13 (a ULK1 complex component), Omegasomes and LC3 establishes and annotates for the first time a complete sequence of steps leading to autophagosome formation, as follows. Upon starvation, the ULK1 complex forms puncta associated with the ER and sporadically with mitochondria. If PtdIns3P is available, these puncta become Omegasomes. Subsequently, the ULK1 complex exits Omegasomes and autophagosomes bud off. If PtdIns3P is unavailable, ULK1 puncta are greatly reduced in number and duration. Atg13 contains a region with affinity for acidic phospholipids, required for translocation to punctate structures and autophagy progression.
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Live Cell Imaging of Early Autophagy Events: Omegasomes and Beyond
Journal of visualized experiments : JoVE, 2013Co-Authors: Eleftherios Karanasios, Maria Manifava, Simon Walker, Eloise Stapleton, Nicholas T KtistakisAbstract:Autophagy is a cellular response triggered by the lack of nutrients, especially the absence of amino acids. Autophagy is defined by the formation of double membrane structures, called autophagosomes, that sequester cytoplasm, long-lived proteins and protein aggregates, defective organelles, and even viruses or bacteria. Autophagosomes eventually fuse with lysosomes leading to bulk degradation of their content, with the produced nutrients being recycled back to the cytoplasm. Therefore, autophagy is crucial for cell homeostasis, and dysregulation of autophagy can lead to disease, most notably neurodegeneration, ageing and cancer. Autophagosome formation is a very elaborate process, for which cells have allocated a specific group of proteins, called the core autophagy machinery. The core autophagy machinery is functionally complemented by additional proteins involved in diverse cellular processes, e.g. in membrane trafficking, in mitochondrial and lysosomal biology. Coordination of these proteins for the formation and degradation of autophagosomes constitutes the highly dynamic and sophisticated response of autophagy. Live cell imaging allows one to follow the molecular contribution of each autophagy-related protein down to the level of a single autophagosome formation event and in real time, therefore this technique offers a high temporal and spatial resolution. Here we use a cell line stably expressing GFP-DFCP1, to establish a spatial and temporal context for our analysis. DFCP1 marks Omegasomes, which are precursor structures leading to autophagosomes formation. A protein of interest (POI) can be marked with either a red or cyan fluorescent tag. Different organelles, like the ER, mitochondria and lysosomes, are all involved in different steps of autophagosome formation, and can be marked using a specific tracker dye. Time-lapse microscopy of autophagy in this experimental set up, allows information to be extracted about the fourth dimension, i.e. time. Hence we can follow the contribution of the POI to autophagy in space and time.
Makoto Naito - One of the best experts on this subject based on the ideXlab platform.
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phosphatidylinositol 3 phosphatase myotubularin related protein 6 mtmr6 is regulated by small gtpase rab1b in the early secretory and autophagic pathways
Journal of Biological Chemistry, 2013Co-Authors: Yasuhiro Mochizuki, Riuko Ohashi, Makoto Naito, Hiroko Iwanari, Tatsuhiko Kodama, Takeshi Kawamura, Takao HamakuboAbstract:Abstract A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular Omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.
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phosphatidylinositol 3 phosphatase myotubularin related protein 6 mtmr6 is regulated by small gtpase rab1b in the early secretory and autophagic pathways
Journal of Biological Chemistry, 2013Co-Authors: Yasuhiro Mochizuki, Riuko Ohashi, Makoto Naito, Hiroko Iwanari, Tatsuhiko Kodama, Takeshi Kawamura, Takao HamakuboAbstract:Abstract A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular Omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.
