10 research outputs found

    Dual binding motifs underpin the hierarchical association of perilipins1-3 with lipid droplets.

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    Lipid droplets (LDs) in all eukaryotic cells are coated with at least one of the perilipin family of proteins. They all regulate key intracellular lipases but do so to significantly different extents. Where more than one perilipin is expressed in a cell, they associate with LDs in a hierarchical manner. In vivo, this means that lipid flux control in a particular cell or tissue type is heavily influenced by the specific perilipins present on its LDs. Despite their early discovery, exactly how perilipins target LDs and why they displace each other in a ‘hierarchical’ manner remains unclear. They all share an amino-terminal 11-mer repeat amphipathic region suggested to be involved in LD targeting. Here, we show that in vivo this domain functions as a primary highly reversible LD targeting motif in perilipins1-3 and, in vitro, we document reversible and competitive binding between a wildtype purified perilipin1 11-mer repeat peptide and a mutant with reduced binding affinity to both ‘naked’ and phospholipid coated oil-water interfaces. We also present data suggesting that a second carboxy-terminal 4-helix bundle domain stabilizes LD binding in perilipin1 more effectively than in perilipin2, whereas in perilipin3 it weakens binding. These findings suggest that dual amphipathic helical regions mediat

    Membrane asymmetry imposes directionality on lipid droplet emergence from the ER

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    During energy bursts, neutral lipids fabricated within the ER bilayer demix to form lipid droplets (LDs). LDs bud off mainly in the cytosol where they regulate metabolism and multiple biological processes. They indeed become accessible to most enzymes and can interact with other organelles. How such directional emergence is achieved remains elusive. Here, we found that this directionality is controlled by an asymmetry in monolayer surface coverage. Model LDs emerge on the membrane leaflet of higher coverage, which is improved by the insertion of proteins and phospholipids. In cells, continuous LD emergence on the cytosol would require a constant refill of phospholipids to the ER cytosolic leaflet. Consistent with this model, cells deficient in phospholipids present an increased number of LDs exposed to the ER lumen and compensate by remodeling ER shape. Our results reveal an active cooperation between phospholipids and proteins to extract LDs from ER

    Dual binding motifs underpin the hierarchical association of perilipins1-3 with lipid droplets.

    No full text
    Lipid droplets (LDs) in all eukaryotic cells are coated with at least one of the perilipin (Plin) family of proteins. They all regulate key intracellular lipases but do so to significantly different extents. Where more than one Plin is expressed in a cell, they associate with LDs in a hierarchical manner. In vivo, this means that lipid flux control in a particular cell or tissue type is heavily influenced by the specific Plins present on its LDs. Despite their early discovery, exactly how Plins target LDs and why they displace each other in a "hierarchical" manner remains unclear. They all share an amino-terminal 11-mer repeat (11mr) amphipathic region suggested to be involved in LD targeting. Here, we show that, in vivo, this domain functions as a primary highly reversible LD targeting motif in Plin1-3, and, in vitro, we document reversible and competitive binding between a wild-type purified Plin1 11mr peptide and a mutant with reduced binding affinity to both "naked" and phospholipid-coated oil-water interfaces. We also present data suggesting that a second carboxy-terminal 4-helix bundle domain stabilizes LD binding in Plin1 more effectively than in Plin2, whereas it weakens binding in Plin3. These findings suggest that dual amphipathic helical regions mediate LD targeting and underpin the hierarchical binding of Plin1-3 to LDs

    Papulose bowenóide: um aspecto clínico da infecção pelo HPV Bowenoid papulosis: a clinical feature of the HPV infection

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    Papulose bowenĂłide Ă© uma doença que acomete a pele da regiĂŁo anogenital e que se caracteriza pelas mĂșltiplas pequenas pĂĄpulas planas ou aveludadas e de coloração que varia do rĂłseo ao castanho-escuro. É provocada pelo HPV e a transmissĂŁo sexual Ă© a forma mais freqĂŒente de contaminação. As queixas mais comuns sĂŁo prurido e dor. O aspecto Ă© caracterĂ­stico e o exame histopatolĂłgico confirma o diagnĂłstico. Junto com a doença de Bowen e a eritroplasia de Queyrat, Ă© considerada como carcinoma in situ, ou neoplasia intra-epitelial de alto grau (NIAA), a lesĂŁo precursora do carcinoma espinocelular (CEC) anal. Sem tratamento, a maioria das lesĂ”es permanece benigna e estĂĄvel. VĂĄrias modalidades terapĂȘuticas estĂŁo disponĂ­veis, incluindo as medicaçÔes tĂłpicas para citodestruição e as tĂ©cnicas ablativas. Os esquemas tĂłpicos sĂŁo efetivos. Cabe ao profissional mĂ©dico escolher a terapia adequada, tendo em mente que a doença Ă© benigna e raramente evolui para carcinoma. Como as recidivas sĂŁo freqĂŒentes e ainda persistem dĂșvidas quanto ao potencial de malignização, os doentes devem ser examinados periodicamente para diagnosticar as lesĂ”es iniciais.<br>Bowenoid papulosis is an anogenital skin disease characterized by multiple little papules, flat or velvet, which color varies from pink to dark brown. It is provoked by HPV and its transmission is sexual. Most common symptoms are anal pain and itching. Its appearance is characteristic and hystopathological examination confirms diagnosis. Together with BowenÂŽs disease and Queyrat erythroplasia, is considered as an in situ carcinoma, or high grade intra-epithelial neoplasia (HAIN), a precursor of the squamous-cell carcinoma. Most of lesions remain benign and stable without treatment. There are several kinds of treatment including topical drugs for cytodestruction and ablative techniques. Topic schemes are effectives. The consultant doctor may choose the most adequate therapy, keeping in mind this disease is benign and rarely evolutes to invasive carcinoma. As recurrences are frequent and remain doubts about malign potential, patients must be examined periodically to diagnose initial lesions
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