Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes.
Reads0
Chats0
TLDR
The real-time behavior of microtubule-associated protein light chain 3 (LC3), which localizes to autophagosomes, is observed, and it is shown that autphagosomes move in a micro Tubule- and dynein-dynactin motor complex-dependent manner.Abstract:
Autophagy is a membrane trafficking pathway that carries cytosolic components to the lysosome for degradation. During this process, the autophagosome, a double-membraned organelle, is generated de novo, sequesters cytoplasmic proteins and organelles, and delivers them to lysosomes. However, the mechanism by which autophagosomes are targeted to lysosomes has not been determined. Here, we observed the real-time behavior of microtubule-associated protein light chain 3 (LC3), which localizes to autophagosomes, and showed that autophagosomes move in a microtubule- and dynein-dynactin motor complex-dependent manner. After formation, autophagosomes show a rapid vectorial movement in the direction of the centrosome, where lysosomes are usually concentrated. Microinjection of antibodies against LC3 inhibited this movement; furthermore, using FRAP, we showed that anti-LC3 antibody injection caused a defect in targeting of autophagosomes to lysosomes. Collectively, our data demonstrate the functional significance of autophagosome movement that enables effective delivery from the cytosol to lysosomes.read more
Citations
More filters
Journal ArticleDOI
Methods in Mammalian Autophagy Research
TL;DR: Methods to monitor autophagy and to modulate autophagic activity are discussed, with a primary focus on mammalian macroautophagy.
Journal ArticleDOI
The role of autophagy in neurodegenerative disease
TL;DR: An overview of the role of autophagy in neurodegenerative disease is provided, focusing particularly on less frequently considered lysosomal clearance mechanisms and their considerable impact on disease.
Journal ArticleDOI
Regulation of Mammalian Autophagy in Physiology and Pathophysiology
Brinda Ravikumar,Sovan Sarkar,Janet E. Davies,Marie Futter,Moisés García-Arencibia,Zeyn W. Green-Thompson,Maria Jimenez-Sanchez,Viktor I. Korolchuk,Maike Lichtenberg,Shouqing Luo,Dunecan Massey,Fiona M. Menzies,Kevin Moreau,Usha Narayanan,Maurizio Renna,Farah H. Siddiqi,Benjamin R. Underwood,Ashley R. Winslow,David C. Rubinsztein +18 more
TL;DR: This review focuses on mammalian autophagy, and an overview of the understanding of its machinery and the signaling cascades that regulate it is given, and the possibility of autophagic upregulation as a therapeutic approach for various conditions is considered.
Journal ArticleDOI
Autophagy modulation as a potential therapeutic target for diverse diseases
TL;DR: An overview of the mechanisms and regulation of autophagy, the role of this pathway in disease and strategies for therapeutic modulation is provided.
Journal ArticleDOI
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages
Kohichi Matsunaga,Tatsuya Saitoh,Keisuke Tabata,Hiroko Omori,Takashi Satoh,Naoki Kurotori,Ikuko Maejima,Kanae Shirahama-Noda,Tohru Ichimura,Toshiaki Isobe,Shizuo Akira,Takeshi Noda,Tamotsu Yoshimori +12 more
TL;DR: The data suggest that the Beclin 1–hVps34 complex functions in two different steps of autophagy by altering the subunit composition, as well as enhancement of endocytic trafficking.
References
More filters
Journal ArticleDOI
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing
Yukiko Kabeya,Noboru Mizushima,Noboru Mizushima,Takashi Ueno,Akitsugu Yamamoto,Takayoshi Kirisako,Takayoshi Kirisako,Takeshi Noda,Takeshi Noda,Eiki Kominami,Yoshinori Ohsumi,Yoshinori Ohsumi,Tamotsu Yoshimori,Tamotsu Yoshimori +13 more
TL;DR: It is demonstrated that the rat microtubule‐associated protein 1 light chain 3 (LC3), a homologue of Apg8p essential for autophagy in yeast, is associated to the autophagosome membranes after processing.
Journal ArticleDOI
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Taichi Hara,Kenji Nakamura,Makoto Matsui,Makoto Matsui,Makoto Matsui,Akitsugu Yamamoto,Yohko Nakahara,Rika Suzuki-Migishima,Minesuke Yokoyama,Kenji Mishima,Ichiro Saito,Hideyuki Okano,Noboru Mizushima +12 more
TL;DR: The results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.
Journal ArticleDOI
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Masaaki Komatsu,Satoshi Waguri,Satoshi Waguri,Tomoki Chiba,Shigeo Murata,Junichi Iwata,Junichi Iwata,Isei Tanida,Takashi Ueno,Masato Koike,Yasuo Uchiyama,Eiki Kominami,Keiji Tanaka +12 more
TL;DR: It is found that mice lacking Atg7 specifically in the central nervous system showed behavioural defects, including abnormal limb-clasping reflexes and a reduction in coordinated movement, and died within 28 weeks of birth, and that impairment of autophagy is implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin-containing inclusion bodies.
Journal ArticleDOI
Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3
TL;DR: Using this method, evidence that overexpression of a dominant negative form of Rab7 prevented the fusion of autophagosomes with lysosomes is provided, suggesting that Rab7 is involved in this step.
Journal ArticleDOI
A ubiquitin-like system mediates protein lipidation
Yoshinobu Ichimura,Takayoshi Kirisako,Takayoshi Kirisako,Toshifumi Takao,Yoshinori Satomi,Yasutsugu Shimonishi,Naotada Ishihara,Noboru Mizushima,Noboru Mizushima,Isei Tanida,Eiki Kominami,Mariko Ohsumi,Takeshi Noda,Takeshi Noda,Yoshinori Ohsumi,Yoshinori Ohsumi +15 more
TL;DR: A new mode of protein lipidation is reported, in which Apg8 is covalently conjugated to phosphatidylethanolamine through an amide bond between the C-terminal glycine and the amino group of phosph atidyleanolamine, mediated by a ubiquitination-like system.