Lipid Sorting and Multivesicular Endosome Biogenesis

Bissig, Christin; Grüenberg, Jean

doi:10.1101/cshperspect.a016816

Cited by 128 publications

(112 citation statements)

References 169 publications

(223 reference statements)

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“…We postulate that in the same manner, PtdInsP binding can recruit IDE to subcellular locations through binding at the polyanion site. In particular, the binding to immobilized PtdIns(3) P is consistent with initial recruitment to early endosomes (22,31,57), and this possibility is supported by our finding that wortmannin treatment, which reduces PtdIns(3)P levels, decreases IDE localization to endosomes (Table 5). Binding to PtdIns(3,4)P2 also would cause early endosome localization, because this phospholipid is present in vesicles just after endocytosis.…”

Section: Ide Localization To Endosomes Involves the Polyanion-bindingsupporting

confidence: 79%

“…Given that IDE has been reported to be present in endosomes (23)(24)(25), we hypothesized that the enzyme initially might be recruited to endosomes by binding to PtdIns(3)P known to be present in the outer leaflet of the endosomal membrane (21,22,31). Discontinuous sucrose density centrifugation was used to enrich endosomes from COS-1 cells as described by Jang et al (32).…”

Section: Ide Localization To Endosomes Involves the Polyanion-bindingmentioning

confidence: 99%

See 1 more Smart Citation

Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes

Song

Jang

Guo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Insulin-degrading enzyme (IDE) hydrolyzes bioactive peptides, including insulin, amylin, and the amyloid β peptides. Polyanions activate IDE toward some substrates, yet an endogenous polyanion activator has not yet been identified. Here we report that inositol phosphates (InsPs) and phosphatdidylinositol phosphates (PtdInsPs) serve as activators of IDE. InsPs and PtdInsPs interact with the polyanion-binding site located on an inner chamber wall of the enzyme. InsPs activate IDE by up to ∼95-fold, affecting primarily V max . The extent of activation and binding affinity correlate with the number of phosphate groups on the inositol ring, with phosphate positional effects observed. IDE binds PtdInsPs from solution, immobilized on membranes, or presented in liposomes. Interaction with PtdInsPs, likely PtdIns(3)P, plays a role in localizing IDE to endosomes, where the enzyme reportedly encounters physiological substrates. Thus, InsPs and PtdInsPs can serve as endogenous modulators of IDE activity, as well as regulators of its intracellular spatial distribution.insulin-degrading enzyme | inositols | phosphatidylinositols | activation | subcellular localization I nsulin-degrading enzyme (IDE), also known as insulysin (EC 3.4.24.56), hydrolyzes a broad range of bioactive peptides in vitro, including angiotensin, glucagon, β-endorphin, amylin, and amyloid β peptides (Aβ), with the two most established in vivo substrates being insulin and Aβ. Evidence supporting a role for IDE in degrading insulin and Aβ in vivo includes associations of IDE gene variants with type 2 diabetes (1, 2) and Alzheimer's disease (3, 4), decreased clearance of the two peptides in IDE-deficient mice (5, 6), and antidiabetic activity produced by IDE inhibitors (7, 8), although some reports have questioned its role in insulin degradation (9, 10). In addition, IDE has been reported to have noncatalytic functions, such as acting as a receptor for varicella-zoster virus (11) and serving as a heat shock protein in stressed cells (12). IDE also modulates the activity of the proteasome (13), reportedly in conjunction with the retinoblastoma tumor-suppressor protein (14).We previously established that polyanions, such as free ATP and triphosphate, increase IDE activity by up to 100-fold toward a synthetic peptide substrate (15) and that ATP binds to a strongly electropositive inner surface of IDE that forms one-half of the substrate-binding chamber (16,17). Significantly, mutations in IDE that reduce its activation by polyanions also decrease its ability to rescue production of a mature yeast mating factor, indicating that activation by polyanions plays an important physiological role in cells (16). Physiological polyanionic activators of IDE have not yet been identified, however.Inositol phosphates (InsPs) are important intracellular second messengers generated by activation of many cell surface receptors (18,19). Phosphatidylinositol phosphates (PtdInsPs; phosphoinositides) participate in signaling and help define the identity of subcellular compartment...

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Section: Ide Localization To Endosomes Involves the Polyanion-bindingsupporting

confidence: 79%

Section: Ide Localization To Endosomes Involves the Polyanion-bindingmentioning

confidence: 99%

Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes

Song

Jang

Guo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Several articles are then devoted to the signals and mechanisms governing these sorting decisions. They cover the molecular machineries responsible for the compartmental organization and function of endosomes (WandingerNess and Zerial 2014) and sorting and transport along endolysosomal pathways (Bissig and Gruenberg 2013;Henne et al 2013;Burd and Cullen 2014;Piper et al 2014). Lysosomes and lysosome-related organelles are discussed in the article by Luzio et al 2014).…”

Section: Overview Of Articlesmentioning

confidence: 99%

Endocytosis: Past, Present, and Future

Schmid

Sorkin

Zerial

2014

Cold Spring Harbor Perspectives in Biology

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“…There has been evidence that phosphoinositides are enriched on specific subcellular membranes. For example, a substantial pool of PtdIns (4)P is present at the Golgi complex, where various PtdIns(4)P effectors have also been identified , whereas PtdIns(3)P and PtdIns(3,5)P 2 are main phosphoinositide messengers at early and late endosomes, respectively, with important roles in the membrane/protein trafficking at the endosomal system (Bissig and Gruenberg, 2013).…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of PtdIns(4,5)P2 – beyond the plasma membrane

Tan

Thapa

Choi

et al. 2015

Journal of Cell Science

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Phosphoinositides are a collection of lipid messengers that regulate most subcellular processes. Amongst the seven phosphoinositide species, the roles for phosphatidylinositol 4,5-bisphosphate [PtdIns (4,5)P 2 ] at the plasma membrane, such as in endocytosis, exocytosis, actin polymerization and focal adhesion assembly, have been extensively studied. Recent studies have argued for the existence of PtdIns(4,5)P 2 at multiple intracellular compartments, including the nucleus, endosomes, lysosomes, autolysosomes, autophagic precursor membranes, ER, mitochondria and the Golgi complex. Although the generation, regulation and functions of PtdIns(4,5)P 2 are less well-defined in most other intracellular compartments, accumulating evidence demonstrates crucial roles for PtdIns(4,5)P 2 in endolysosomal trafficking, endosomal recycling, as well as autophagosomal pathways, which are the focus of this Commentary. We summarize and discuss how phosphatidylinositol phosphate kinases, PtdIns(4,5)P 2 and PtdIns(4,5)P 2 -effectors regulate these intracellular protein and membrane trafficking events.

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Lipid Sorting and Multivesicular Endosome Biogenesis

Cited by 128 publications

References 169 publications

Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes

Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes

Endocytosis: Past, Present, and Future

Emerging roles of PtdIns(4,5)P2 – beyond the plasma membrane

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