Phosphoinositide synthesis and degradation in isolated rat liver peroxisomes

Jeynov, Boyan; Lay, Dorothee; Schmidt, F.H.; Tahirović, Sabina; Just, Wilhelm W.

doi:10.1016/j.febslet.2006.09.058

Cited by 26 publications

(27 citation statements)

References 46 publications

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“…Syt7-C2AB mainly bound PI(4,5)P 2 and to a much lesser extent PI(5)P and PS; no signal was observed for other phospholipids ( Figure 5A). It has been reported that peroxisome can synthesize significant amounts of PIP2 including PI(4,5)P 2 (Jeynov et al, 2006). To further validate Syt7-PI(4,5)P 2 interaction under a more relevant format, we performed the liposome flotation assay using liposomes mimicking phospholipid composition of the mammalian peroxisome membrane (PC:PE:PI:PS = 54:36:5:5) (Hardeman et al, 1990).…”

Section: Synaptotagmin VII Is a Lysosomal Protein Binding Peroxisomementioning

confidence: 99%

Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts

Chu

Liao

et al. 2015

Cell

332

297

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Cholesterol is dynamically transported among organelles, which is essential for multiple cellular functions. However, the mechanism underlying intracellular cholesterol transport has remained largely unknown. We established an amphotericin B-based assay enabling a genome-wide shRNA screen for delayed LDL-cholesterol transport and identified 341 hits with particular enrichment of peroxisome genes, suggesting a previously unappreciated pathway for cholesterol transport. We show dynamic membrane contacts between peroxisome and lysosome, which are mediated by lysosomal Synaptotagmin VII binding to the lipid PI(4,5)P2 on peroxisomal membrane. LDL-cholesterol enhances such contacts, and cholesterol is transported from lysosome to peroxisome. Disruption of critical peroxisome genes leads to cholesterol accumulation in lysosome. Together, these findings reveal an unexpected role of peroxisome in intracellular cholesterol transport. We further demonstrate massive cholesterol accumulation in human patient cells and mouse model of peroxisomal disorders, suggesting a contribution of abnormal cholesterol accumulation to these diseases.

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Section: Synaptotagmin VII Is a Lysosomal Protein Binding Peroxisomementioning

confidence: 99%

Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts

Chu

Liao

et al. 2015

Cell

332

297

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“…3H and I) and pex14p (not shown) [44], [45]. Peroxisomes have a unique PtdInsPs system [46], but there is no established treatment for modulating their PtdInsPs levels. The treatments we attempted, wortmannin and LY294002, affecting PtdIns3P levels, and ionomycin, reducing PtdIns(4,5)P2 levels, did not alter the peroxisomal enrichments of the fluorescent proteins.…”

Section: Resultsmentioning

confidence: 99%

Prevalence, Specificity and Determinants of Lipid-Interacting PDZ Domains from an In-Cell Screen and In Vitro Binding Experiments

et al. 2013

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BackgroundPDZ domains are highly abundant protein-protein interaction modules involved in the wiring of protein networks. Emerging evidence indicates that some PDZ domains also interact with phosphoinositides (PtdInsPs), important regulators of cell polarization and signaling. Yet our knowledge on the prevalence, specificity, affinity, and molecular determinants of PDZ-PtdInsPs interactions and on their impact on PDZ-protein interactions is very limited.Methodology/Principal FindingsWe screened the human proteome for PtdInsPs interacting PDZ domains by a combination of in vivo cell-localization studies and in vitro dot blot and Surface Plasmon Resonance (SPR) experiments using synthetic lipids and recombinant proteins. We found that PtdInsPs interactions contribute to the cellular distribution of some PDZ domains, intriguingly also in nuclear organelles, and that a significant subgroup of PDZ domains interacts with PtdInsPs with affinities in the low-to-mid micromolar range. In vitro specificity for the head group is low, but with a trend of higher affinities for more phosphorylated PtdInsPs species. Other membrane lipids can assist PtdInsPs-interactions. PtdInsPs-interacting PDZ domains have generally high pI values and contain characteristic clusters of basic residues, hallmarks that may be used to predict additional PtdInsPs interacting PDZ domains. In tripartite binding experiments we established that peptide binding can either compete or cooperate with PtdInsPs binding depending on the combination of ligands.Conclusions/SignificanceOur screen substantially expands the set of PtdInsPs interacting PDZ domains, and shows that a full understanding of the biology of PDZ proteins will require a comprehensive insight into the intricate relationships between PDZ domains and their peptide and lipid ligands.

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“…By phosphorylation of the myosin-binding subunit of myosin phosphatase and/or the myosin light chain of myosin II, ROCKII enhances myosin ATPase activity [47], [48]. Moreover, ROCKII contains a well-defined pleckstrin homology domain binding to PtdIns(4,5)P 2 the synthesis of which in the peroxisomal membrane was recently reported [49].…”

Section: Discussionmentioning

confidence: 97%

RhoA Regulates Peroxisome Association to Microtubules and the Actin Cytoskeleton

et al. 2010

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The current view of peroxisome inheritance provides for the formation of new peroxisomes by both budding from the endoplasmic reticulum and autonomous division. Here we investigate peroxisome-cytoskeleton interactions and show by proteomics, biochemical and immunofluorescence analyses that actin, non-muscle myosin IIA (NMM IIA), RhoA, Rho kinase II (ROCKII) and Rab8 associate with peroxisomes. Our data provide evidence that (i) RhoA in its inactive state, maintained for example by C. botulinum toxin exoenzyme C3, dissociates from peroxisomes enabling microtubule-based peroxisomal movements and (ii) dominant-active RhoA targets to peroxisomes, uncouples the organelles from microtubules and favors Rho kinase recruitment to peroxisomes. We suggest that ROCKII activates NMM IIA mediating local peroxisomal constrictions. Although our understanding of peroxisome-cytoskeleton interactions is still incomplete, a picture is emerging demonstrating alternate RhoA-dependent association of peroxisomes to the microtubular and actin cytoskeleton. Whereas association of peroxisomes to microtubules clearly serves bidirectional, long-range saltatory movements, peroxisome-acto-myosin interactions may support biogenetic functions balancing peroxisome size, shape, number, and clustering.

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Phosphoinositide synthesis and degradation in isolated rat liver peroxisomes

Cited by 26 publications

References 46 publications

Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts

Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts

Prevalence, Specificity and Determinants of Lipid-Interacting PDZ Domains from an In-Cell Screen and In Vitro Binding Experiments

RhoA Regulates Peroxisome Association to Microtubules and the Actin Cytoskeleton

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