scholarly journals Regulation of autophagic activity by 14-3-3ζ proteins associated with class III phosphatidylinositol-3-kinase

2010 ◽  
Vol 18 (3) ◽  
pp. 479-492 ◽  
Author(s):  
M Pozuelo-Rubio
Keyword(s):  
Class Iii ◽  
Phosphatidylinositol 3 Kinase ◽  
Autophagic Activity ◽  
Phosphatidylinositol 3

scholarly journals Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complex

2009 ◽  
Vol 11 (4) ◽  
pp. 468-476 ◽  
Author(s):  
Yun Zhong ◽  
Qing Jun Wang ◽  
Xianting Li ◽  
Ying Yan ◽  
Jonathan M. Backer ◽  
...  
Keyword(s):  
Beclin 1 ◽  
Phosphatidylinositol 3 Kinase ◽  
Autophagic Activity ◽  
Phosphatidylinositol 3

scholarly journals Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAG

2008 ◽  
Vol 19 (12) ◽  
pp. 5360-5372 ◽  
Author(s):  
Eisuke Itakura ◽  
Chieko Kishi ◽  
Kinji Inoue ◽  
Noboru Mizushima
Keyword(s):  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Coiled Coil ◽  
Pi3 Kinase ◽  
Beclin 1 ◽  
Class Iii ◽  
Phosphatidylinositol 3 Kinase ◽  
Interacting Protein ◽  
Vacuolar Protein ◽  
Phosphatidylinositol 3

Class III phosphatidylinositol 3-kinase (PI3-kinase) regulates multiple membrane trafficking. In yeast, two distinct PI3-kinase complexes are known: complex I (Vps34, Vps15, Vps30/Atg6, and Atg14) is involved in autophagy, and complex II (Vps34, Vps15, Vps30/Atg6, and Vps38) functions in the vacuolar protein sorting pathway. Atg14 and Vps38 are important in inducing both complexes to exert distinct functions. In mammals, the counterparts of Vps34, Vps15, and Vps30/Atg6 have been identified as Vps34, p150, and Beclin 1, respectively. However, orthologues of Atg14 and Vps38 remain unknown. We identified putative mammalian homologues of Atg14 and Vps38. The Vps38 candidate is identical to UV irradiation resistance-associated gene (UVRAG), which has been reported as a Beclin 1-interacting protein. Although both human Atg14 and UVRAG interact with Beclin 1 and Vps34, Atg14, and UVRAG are not present in the same complex. Although Atg14 is present on autophagic isolation membranes, UVRAG primarily associates with Rab9-positive endosomes. Silencing of human Atg14 in HeLa cells suppresses autophagosome formation. The coiled-coil region of Atg14 required for binding with Vps34 and Beclin 1 is essential for autophagy. These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways.

scholarly journals Ca2+-regulated Pool of Phosphatidylinositol-3-phosphate Produced by Phosphatidylinositol 3-Kinase C2α on Neurosecretory Vesicles

2008 ◽  
Vol 19 (12) ◽  
pp. 5593-5603 ◽  
Author(s):  
Peter J. Wen ◽  
Shona L. Osborne ◽  
Isabel C. Morrow ◽  
Robert G. Parton ◽  
Jan Domin ◽  
...  
Keyword(s):  
Critical Role ◽  
Neurosecretory Cells ◽  
Secretory Vesicles ◽  
Endosomal Trafficking ◽  
Class Iii ◽  
Phosphatidylinositol 3 Kinase ◽  
Lipid Product ◽  
Phosphatidylinositol 3

Phosphatidylinositol-3-phosphate [PtdIns(3)P] is a key player in early endosomal trafficking and is mainly produced by class III phosphatidylinositol 3-kinase (PI3K). In neurosecretory cells, class II PI3K-C2α and its lipid product PtdIns(3)P have recently been shown to play a critical role during neuroexocytosis, suggesting that two distinct pools of PtdIns(3)P might coexist in these cells. However, the precise characterization of this additional pool of PtdIns(3)P remains to be established. Using a selective PtdIns(3)P probe, we have identified a novel PtdIns(3)P-positive pool localized on secretory vesicles, sensitive to PI3K-C2α knockdown and relatively resistant to wortmannin treatment. In neurosecretory cells, stimulation of exocytosis promoted a transient albeit large increase in PtdIns(3)P production localized on secretory vesicles sensitive to PI3K-C2α knockdown and expression of PI3K-C2α catalytically inactive mutant. Using purified chromaffin granules, we found that PtdIns(3)P production is controlled by Ca2+. We confirmed that PtdIns(3)P production from recombinantly expressed PI3K-C2α is indeed regulated by Ca2+. We provide evidence that a dynamic pool of PtdIns(3)P synthesized by PI3K-C2α occurs on secretory vesicles in neurosecretory cells, demonstrating that the activity of a member of the PI3K family is regulated by Ca2+ in vitro and in living neurosecretory cells.

Possible involvement of Class III phosphatidylinositol-3-kinase in meiotic progression of porcine oocytes beyond germinal vesicle stage

2011 ◽  
Vol 75 (5) ◽  
pp. 940-950 ◽  
Author(s):  
Myung Rae Park ◽  
Mukesh Kumar Gupta ◽  
Hye Ran Lee ◽  
Ziban Chandra Das ◽  
Sang Jun Uhm ◽  
...  
Keyword(s):  
Germinal Vesicle ◽  
Class Iii ◽  
Phosphatidylinositol 3 Kinase ◽  
Meiotic Progression ◽  
Phosphatidylinositol 3

scholarly journals Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy

2016 ◽  
Vol 113 (29) ◽  
pp. 8224-8229 ◽  
Author(s):  
Lindsey N. Young ◽  
Kelvin Cho ◽  
Rosalie Lawrence ◽  
Roberto Zoncu ◽  
James H. Hurley
Keyword(s):  
Complex I ◽  
Class Iii ◽  
Phosphatidylinositol 3 Kinase ◽  
Lipid Kinase ◽  
Negative Stain ◽  
Binding Factor ◽  
Hydrogen Deuterium ◽  
Negative Stain Electron Microscopy ◽  
Vacuolar Protein ◽  
Phosphatidylinositol 3

The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) is central to autophagy initiation. We previously reported the V-shaped architecture of the four-subunit version of PI3KC3-C1 consisting of VPS (vacuolar protein sorting) 34, VPS15, BECN1 (Beclin 1), and ATG (autophagy-related) 14. Here we show that a putative fifth subunit, nuclear receptor binding factor 2 (NRBF2), is a tightly bound component of the complex that profoundly affects its activity and architecture. NRBF2 enhances the lipid kinase activity of the catalytic subunit, VPS34, by roughly 10-fold. We used hydrogen–deuterium exchange coupled to mass spectrometry and negative-stain electron microscopy to map NRBF2 to the base of the V-shaped complex. NRBF2 interacts primarily with the N termini of ATG14 and BECN1. We show that NRBF2 is a homodimer and drives the dimerization of the larger PI3KC3-C1 complex, with implications for the higher-order organization of the preautophagosomal structure.

scholarly journals Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity

2013 ◽  
Vol 203 (2) ◽  
pp. 299-313 ◽  
Author(s):  
Yasuhiro Araki ◽  
Wei-Chi Ku ◽  
Manami Akioka ◽  
Alexander I. May ◽  
Yu Hayashi ◽  
...  
Keyword(s):  
Complex I ◽  
Protein Complexes ◽  
Pi3 Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
C Terminus ◽  
Physical Linkage ◽  
N Terminus ◽  
Autophagic Activity ◽  
Biochemical Analyses ◽  
Phosphatidylinositol 3

Autophagy is a conserved eukaryotic process of protein and organelle self-degradation within the vacuole/lysosome. Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. In yeast, Vps34 forms two distinct protein complexes: complex I, which functions in autophagy, and complex II, which is involved in protein sorting to the vacuole. Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Δ cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15–Vps34 and Atg14–Vps30 subcomplexes. We find that Atg38 physically interacted with Atg14 and Vps34 via its N terminus. Further biochemical analyses revealed that Atg38 homodimerizes through its C terminus and that this homodimer formation is indispensable for the integrity of complex I. These data suggest that the homodimer of Atg38 functions as a physical linkage between the Vps15–Vps34 and Atg14–Vps30 subcomplexes to facilitate complex I formation.

scholarly journals Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1

2012 ◽  
Vol 23 (15) ◽  
pp. 2955-2962 ◽  
Author(s):  
Dave Bridges ◽  
Jing-Tyan Ma ◽  
Sujin Park ◽  
Ken Inoki ◽  
Lois S. Weisman ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Target Of Rapamycin ◽  
Class Iii ◽  
Cell Type ◽  
Phosphatidylinositol 3 Kinase ◽  
Mechanistic Target Of Rapamycin ◽  
Cell Type Specific ◽  
Stepwise Formation ◽  
Phosphatidylinositol 3

The kinase complex mechanistic target of rapamycin 1 (mTORC1) plays an important role in controlling growth and metabolism. We report here that the stepwise formation of phosphatidylinositol 3-phosphate (PI(3)P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) regulates the cell type–specific activation and localization of mTORC1. PI(3)P formation depends on the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α, as well as the class III PI3K Vps34, while PI(3,5)P2 requires the phosphatidylinositol-3-phosphate-5-kinase PIKFYVE. In this paper, we show that PIKFYVE and PI3K-C2α are necessary for activation of mTORC1 and its translocation to the plasma membrane in 3T3-L1 adipocytes. Furthermore, the mTORC1 component Raptor directly interacts with PI(3,5)P2. Together these results suggest that PI(3,5)P2 is an essential mTORC1 regulator that defines the localization of the complex.

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