Core Protein Machinery for Mammalian Phosphatidylinositol 3,5-Bisphosphate Synthesis and Turnover That Regulates the Progression of Endosomal Transport

Sbrissa, Diego; Ikonomov, Ognian C.; Fu, Zhiyao; Ijuin, Takeshi; Grüenberg, Jean; Takenawa, Tadaomi; Shisheva, Assia

doi:10.1074/jbc.m611678200

Cited by 170 publications

(255 citation statements)

References 64 publications

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“…PIKfyve localizes via its FYVE-domain to PI(3)P-positive endosomes. Positive regulation of its activity by Sac3 (Ikonomov, Sbrissa et al 2003;Sbrissa, Ikonomov et al 2007) assures balanced PI(3,5)P 2 synthesis together with a high turnover rate. According to the role of its lipid product PI(3,5)P 2 loss of PIKfyve impairs retrograde endosome-to-Golgi transport and degradative sorting of i.e.…”

Section: Figure 3: Tubular Cargo-enriched Subdomains At the Early Sormentioning

confidence: 99%

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

157

177

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I owe special thanks to Marnix Wieffer and Michael Krauß, who spent a lot of time helping me to get started in the lab, to overcome numerous experimental problem, I was not sure how to deal with, and frequently joined in discussions about my project with excellent advice. I am really grateful for your experimental support, Michael, and the time you invested in the project during our paper revision.Further, I would like to thank Jocelyn Laporte and his group, especially Anne-Sophie Nicot, at the IGBMC in Strasbourg for their support and a very fruitful collaboration, and Carsten Schultz and his group at the EMBL in Heidelberg for their support and constant supply with PIP/AMs. I owe special thanks to Dmytro Puchkov for the ultrastructural analysis and Eberhard Krause for mass spectrometry done within this project. I also need to acknowledge Markus Wenk and Federico Torta at the Singapore Lipidomics Incubator for joining the project at a very late stage, when we urgently needed help from lipidomics specialists. It was a pity that experiments did not work out as planned.I would further like to express my gratitude to two very skilled technicians in the AG Haucke lab: Silke Zillmann and Delia Löwe. Without your help it would have been impossible to achieve so much within the limited amount of time I had during the paper revision. by VPS34-IN1 treatment................................................... 52 2.3.11 Fluorescence microscopy................................................................................. 53 2.3.12 Flow cytometry............................................................................................ III SummaryPhosphoinositides (PIs) are a minor class of short-lived phospholipids that serve as crucial signposts of membrane identity. Thereby, PIs full fill important functions in cell signaling and membrane transport. PI 4-phosphates such as phosphatitylinositol-4-phosphate (PI(4)P) and phosphatitylinositol-4,5-bisphosphate (PI(4,5)P 2 ) are enriched at the plasma membrane (PM), on secretory organelles and lysosomes, while PI 3-phosphates, i.e.phosphatitylinositol-3-phosphate (PI(3)P), are a hallmark of the endosomal system.Directional transport between these compartments, thus, requires regulated PI conversion.However, PI conversion in exit from PI(3)P-enriched endosomes en route to the PI(4)P-and PI(4,5)P 2 -positive PM in endosomal recycling remained unknown.Here, we report that cargo exit from endosomes requires removal of PI(3)P by the PI(3)P 3-phosphatase myotubularin 1 (MTM1), and concomitant PI(4)P synthesis by PI 4-kinase type II α (PI4K2α). Loss of MTM1 causes endosomal accumulation of PI(3)P and PI(3)P effector proteins, i.e. sorting nexins, Kif16b-mediated outward traffic of PI(3)P containing endosomes and sub-plasmalemmal accumulation of exocytosis-deficient endosomes. As PI4K2α associates with MTM1 and thereby facilitates membrane recruitment of MTM1, these phenotypic changes are mimicked by loss of PI4K2α. The conversion of PI(3)P-to-PI(4)P is paralleled by a switch i...

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Section: Figure 3: Tubular Cargo-enriched Subdomains At the Early Sormentioning

confidence: 99%

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

157

177

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“…It might be useful to compare the Fab1 and PIKfyve complexes (Sbrissa et al, 2007). Notably, the union of the kinase and phosphatase activities into one complex is conserved in yeast and mammalian cells.…”

Section: A Lipid Kinase-lipid Phosphatase Complex Thatmentioning

confidence: 99%

“…In yeast, the only established interaction as of yet is between Fig4 and Vac14 (Rudge et al, 2004;Duex et al, 2006b), whereas assays testing for Fab1 interaction with its regulators have thus far been unsuccessful Rudge et al, 2004). In mammals, it is proposed that PIKfyve forms a ternary complex with ArPIKfyve and hSac3, the Vac14 and Fig4 orthologues, respectively (Sbrissa et al, 2007). However, the functional consequence for this complex remains to be examined.…”

Section: Introductionmentioning

confidence: 99%

Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase

Botelho

Efe

Teis

et al. 2008

MBoC

121

191

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“…In yeast and animals, Fab1p/PIKfyve form a protein complex with Fab1 regulatory proteins, Fig4/Sac3 (a lipid phosphatase), Vac7 (a FAB1 activator) and Atg18 (a FAB1 effector), and a scaffold protein, Vac14 (Duex et al, 2006;Efe et al, 2007;Sbrissa et al, 2007;Michell and Dove, 2009). All genes encoding Fab1 complex proteins, except Vac7, have also been found in the Arabidopsis genome.…”

Section: Function Of Arabidopsis Fab1a/b Proteins In Plant Cellsmentioning

confidence: 99%

Loss-of-Function and Gain-of-Function Mutations in FAB1A/B Impair Endomembrane Homeostasis, Conferring Pleiotropic Developmental Abnormalities in Arabidopsis

et al. 2010

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In eukaryotic cells, PtdIns 3,5-kinase, Fab1/PIKfyve produces PtdIns (3,5) P 2 from PtdIns 3-P, and functions in vacuole/ lysosome homeostasis. Herein, we show that expression of Arabidopsis (Arabidopsis thaliana) FAB1A/B in fission yeast (Schizosaccharomyces pombe) fab1 knockout cells fully complements the vacuole morphology phenotype. Subcellular localizations of FAB1A and FAB1B fused with green fluorescent protein revealed that FAB1A/B-green fluorescent proteins localize to the endosomes in root epidermal cells of Arabidopsis. Furthermore, reduction in the expression levels of FAB1A/B by RNA interference impairs vacuolar acidification and endocytosis. These results indicate that Arabidopsis FAB1A/B functions as PtdIns 3,5-kinase in plants and in fission yeast. Conditional knockdown mutant shows various phenotypes including root growth inhibition, hyposensitivity to exogenous auxin, and disturbance of root gravitropism. These phenotypes are observed also in the overproducing mutants of FAB1A and FAB1B. The overproducing mutants reveal additional morphological phenotypes including dwarfism, male-gametophyte sterility, and abnormal floral organs. Taken together, this evidence indicates that imbalanced expression of FAB1A/B impairs endomembrane homeostasis including endocytosis, vacuole formation, and vacuolar acidification, which causes pleiotropic developmental phenotypes mostly related to the auxin signaling in Arabidopsis.

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Core Protein Machinery for Mammalian Phosphatidylinositol 3,5-Bisphosphate Synthesis and Turnover That Regulates the Progression of Endosomal Transport

Cited by 170 publications

References 64 publications

A phosphoinositide conversion mechanism for exit from endosomes

A phosphoinositide conversion mechanism for exit from endosomes

Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase

Loss-of-Function and Gain-of-Function Mutations in FAB1A/B Impair Endomembrane Homeostasis, Conferring Pleiotropic Developmental Abnormalities in Arabidopsis

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