Myotubularin Lipid Phosphatase Binds the hVPS15/hVPS34 Lipid Kinase Complex on Endosomes

Cao, Canhong; Laporte, Jocelyn; Backer, Jonathan M.; Wandinger‐Ness, Angela; Stein, Mary Pat

doi:10.1111/j.1600-0854.2007.00586.x

Cited by 79 publications

(73 citation statements)

References 65 publications

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“…The latter conclusion is corroborated by previous studies on MTM1 localization (Cao, Laporte et al 2007) and further applies to other myotubularins. This indicates a tight regulation of their membrane association and thereby enzymatic activity.…”

Section: Membrane Recruitment Of Mtm1 Is Regulated By Lipid and Protesupporting

confidence: 89%

“…Based on the accumulation of β1-integrin in late and recycling endosomes, compartments where MTM1 was previously found to be localized (Cao, Laporte et al 2007), we reasoned that cargo exit (i.e. β1-integrin or TfR) from endosomes might be defective in XLCNM patients.…”

Section: Impaired Cargo Exit From Endosomes Due To Defective Exocytosismentioning

confidence: 99%

“…According to its PI(3)P and PI(3,5)P 2 3-phosphatase activity, MTM1 localizes to early and late endosomes. Recruitment and PI turnover is thought to be regulated by Vps34 ( Figure 4) (Cao, Laporte et al 2007) and by the phosphatase-inactive MTMR12 (Nandurkar, Layton et al 2003). Targeted recruitment of MTM1 to early endosomes and thereby PI(3)P depletion enhances microtubule-dependent endosome tubulation (Fili, Calleja et al 2006) during endosomal recycling.…”

Section: Mtm1 Regulates Endosomal Pi(3)p Turnover and Membrane Dynamicsmentioning

confidence: 99%

“…Rab11-and Rab14-positive). Most importantly, MTM1 was found on TfRpositive endosomes, while colocalization with the late endosomal/ lysosomal marker LAMP1 or the trans-Golgi-network marker TGN46 was less prominent (Cao, Laporte et al 2007) ( Figure 19). Consistent with its substrate specificity MTM1 preferentially associated with PI(3)P-containing liposomes in flotation assays in vitro while only minor binding to PI(4)Pand PI(4,5)P 2 -over PI-containing control liposomes could be observed (data not shown, experiments performed by Michael Krauß).…”

Section: Mtm1 Localizes To Early and Recycling Endosomesmentioning

confidence: 99%

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A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

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161

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: Membrane Recruitment Of Mtm1 Is Regulated By Lipid and Protesupporting

confidence: 89%

Section: Impaired Cargo Exit From Endosomes Due To Defective Exocytosismentioning

confidence: 99%

Section: Mtm1 Regulates Endosomal Pi(3)p Turnover and Membrane Dynamicsmentioning

confidence: 99%

Section: Mtm1 Localizes To Early and Recycling Endosomesmentioning

confidence: 99%

See 2 more Smart Citations

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

Self Cite

161

177

View full text Add to dashboard Cite

show abstract

“…It is tempting to suggest that PtdIns kinase-phosphatase coupling may be a common mechanism to modulate PtdInsPs. Recently, the mammalian VPS34 PtdIns 3-kinase and the MTM1 PtdIns(3)P 3-phosphatase were shown to interact (Cao et al, 2007). …”

Section: A Lipid Kinase-lipid Phosphatase Complex Thatmentioning

confidence: 99%

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

Botelho

Efe

Teis

et al. 2008

MBoC

123

191

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Changing phosphoinositides “on the fly”: how trafficking vesicles avoid an identity crisis

Botelho

2009

BioEssays

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Joining an antagonistic phosphoinositide (PtdInsP) kinase and phosphatase into a single protein complex may regulate rapid and local PtdInsP changes. This may be important for processes such as membrane fission that require a specific PtdInsP and that are innately local and rapid. Such a complex could couple vesicle formation, with erasing of the identity of the donor organelle from the vesicle prior to its fusion with target organelles, thus preventing organelle identity intermixing. Coordinating signals are postulated to switch the relative activities of the kinase and phosphatase in a spatio-temporal manner that matches membrane fission events. The discovery of two such complexes supports this hypothesis. One regulates the interconversion of phosphatidylinositol and PtdIns(3)P by joining the Vps34 PtdIns 3-kinase and the myotubularin 3-phosphatases. The other regulates the interconversion between PtdIns(3)P and PtdIns(3,5)P(2) through the Fab1/PIKfyve kinase and the Fig4/mFig4 phosphatase. These lipids are essential components of the endosomal identity code.

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Myotubularin Lipid Phosphatase Binds the hVPS15/hVPS34 Lipid Kinase Complex on Endosomes

Cited by 79 publications

References 65 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

Changing phosphoinositides “on the fly”: how trafficking vesicles avoid an identity crisis

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