Phosphatidylinositol 3,5‐Bisphosphate‐Rich Membrane Domains in Endosomes and Lysosomes

Takatori, Sho; Tatematsu, Tsuyako; Cheng, Jinglei; Matsumoto, Jun; Akano, Takuya; Fujimoto, Toyoshi

doi:10.1111/tra.12346

Cited by 37 publications

(39 citation statements)

References 43 publications

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“…Lipid phase separations can drive fission reactions, and they can be promoted or induced by proteins binding to one of the lipid phases. They segregate a liquid-ordered phase that is readily detectable by freeze-fracture EM because it is virtually free of intramembranous particles (bona fide transmembrane proteins) (Müller et al, 2000;Takatori et al, 2016). Also vacuoles undergoing membrane fission show striking lipid phase separation.…”

Section: Discussionmentioning

confidence: 99%

Membrane scission driven by the PROPPIN Atg18

et al. 2017

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Sorting, transport, and autophagic degradation of proteins in endosomes and lysosomes, as well as the division of these organelles, depend on scission of membrane-bound tubulo-vesicular carriers. How scission occurs is poorly understood, but family proteins bind these membranes. Here, we show that the yeast PROPPIN Atg18 carries membrane scission activity. Purified Atg18 drives tubulation and scission of giant unilamellar vesicles. Upon membrane contact, Atg18 folds its unstructured CD loop into an amphipathic α-helix that inserts into the bilayer. This allows the protein to engage its two lipid binding sites for PI3P and PI(3,5)P PI(3,5)P induces Atg18 oligomerization, which should concentrate lipid-inserted α-helices in the outer membrane leaflet and drive membrane tubulation and scission. The scission activity of Atg18 is compatible with its known roles in endo-lysosomal protein trafficking, autophagosome biogenesis, and vacuole fission. Key features required for membrane tubulation and scission by Atg18 are shared by other PROPPINs, suggesting that membrane scission may be a generic function of this protein family.

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Section: Discussionmentioning

confidence: 99%

Membrane scission driven by the PROPPIN Atg18

et al. 2017

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“…PtdIns(3,5) P 2 is a rare PPIn, since it represents less than 5% of total PPIn in S. cerevisiae and human and is enriched in vesicular and tubular domains in late endosomes and at the vacuole (yeast)/lysosome (HeLa cells) (Figure 2) [79,103]. …”

Section: Ptdins(35)p2 a Regulator Of Endosome-lysosome Traffickingmentioning

confidence: 99%

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

Craene

Bertazzi

Bär

et al. 2017

IJMS

171

149

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Abstract:Phosphoinositides are lipids involved in the vesicular transport of proteins and lipids between the different compartments of eukaryotic cells. They act by recruiting and/or activating effector proteins and thus are involved in regulating various cellular functions, such as vesicular budding, membrane fusion and cytoskeleton dynamics. Although detected in small concentrations in membranes, their role is essential to cell function, since imbalance in their concentrations is a hallmark of many cancers. Their synthesis involves phosphorylating/dephosphorylating positions D3, D4 and/or D5 of their inositol ring by specific lipid kinases and phosphatases. This process is tightly regulated and specific to the different intracellular membranes. Most enzymes involved in phosphoinositide synthesis are conserved between yeast and human, and their loss of function leads to severe diseases (cancer, myopathy, neuropathy and ciliopathy).Keywords: lipids; membrane trafficking; vesicles; phosphoinositides; phosphatase; kinase Phosphoinositides in Cellular Membranes Lipids, Major Membrane ComponentsThe dynamic modulation of the physicochemical properties of membranes is required for eukaryotic cells function. Indeed, cells live in an environment characterized by temperature, relative humidity, pH, sun exposure, osmotic pressure and nutrient variations. Living organisms have to adapt to variations of these different factors in order to keep their intracellular balance. Eukaryotic cells have achieved this by adopting a compartmentalized organization, which minimizes the intracellular variations resulting from extracellular fluctuations. The plasma membrane is the first barrier separating the cytoplasm from the extracellular medium. Its composition ensures a mechanical protection, but also allows exchanges with the medium through transporters and receptors, as a form of very selective permeability.Membranes are composed of two phospholipid leaflets organized as a bilayer in which sterols, glycolipids and proteins are inserted. The phospholipids of this bilayer are amphiphilic with a hydrophilic group (head) linked to a hydrophobic group (tail) ( Figure 1A). In the bilayer, the hydrophobic groups face each other, thus creating a hydrophobic space in between them, which ensures its role as a barrier. This property is very important for the anchoring of hydrophobic molecules, such as sterols or ceramides, transmembrane domains or the lipid anchor of proteins. The lipid composition of membranes varies according to the organism (eukaryotes or prokaryotes), the cell type (among the different tissues of a multicellular organism), the membrane type (plasma Int.

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“…developed a method to detect PI(3,5)P 2 combining freeze-fracture electron microscopy with the use of tagged Atg18 protein as a PI(3,5)P 2 binding probe (Takatori et al , 2016). Atg18 binds to both PI(3,5)P 2 and PI3P.…”

Section: Phosphatidylinositol 35-bisphosphate (Pi(35)p2)mentioning

confidence: 99%

PI5P and PI(3,5)P<sub>2</sub>: Minor, but Essential Phosphoinositides

Hasegawa

Strunk

Weisman

2017

Cell Struct. Funct.

127

119

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In most eukaryotes, phosphoinositides (PIs) have crucial roles in multiple cellular functions. Although the cellular levels of phosphatidylinositol 5-phosphate (PI5P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) are extremely low relative to some other PIs, emerging evidence demonstrates that both lipids are crucial for the endocytic pathway, intracellular signaling, and adaptation to stress. Mutations that causes defects in the biosynthesis of PI5P and PI(3,5)P2 are linked to human diseases including neurodegenerative disorders. Here, we review recent findings on cellular roles of PI5P and PI(3,5)P2, as well as the pathophysiological importance of these lipids.

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Phosphatidylinositol 3,5‐Bisphosphate‐Rich Membrane Domains in Endosomes and Lysosomes

Cited by 37 publications

References 43 publications

Membrane scission driven by the PROPPIN Atg18

Membrane scission driven by the PROPPIN Atg18

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

PI5P and PI(3,5)P<sub>2</sub>: Minor, but Essential Phosphoinositides

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