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ARCA - Access to Research and Communication Annals - IGC Repository (791 recursos)

The Institutional Repository of Instituto Gulbenkian de Ciência, developed under the project RCAAP, is intended to collect, preserve and promote open access to the intellectual production of their researchers.

Membrane Traffic in Disease and Novel Therapies

Mostrando recursos 1 - 4 de 4

  1. Phosphonocarboxylates inhibit the second geranylgeranyl addition by Rab geranylgeranyl transferase

    Baron, RA.; Tavare, R.; Figueiredo, AC.; Blazewska, KM.; Kashemirov, BA.; McKenna, CE.; Ebetino, FH.; Taylor, A.; Rogers, MJ.; Coxon, FP.; Seabra, MC.
    Rab geranylgeranyl transferase (RGGT) catalyzes the post-translational geranylgeranyl (GG) modification of (usually) two C-terminal cysteines in Rab GTPases. Here we studied the mechanism of the Rab geranylgeranylation reaction by bisphosphonate analogs in which one phosphonate group is replaced by a carboxylate (phosphonocarboxylate, PC). The phosphonocarboxylates used were 3-PEHPC, which was previously reported, and2-hydroxy-3-imidazo[1,2-a] pyridin-3-yl-2-phosphonopropionic acid ((+)-3-IPEHPC), a >25-fold more potent related compound as measured by both IC50 and Ki. (+)-3-IPEHPC behaves as a mixed-type inhibitor with respect to GG pyrophosphate ( GGPP) and an uncompetitive inhibitor with respect to Rab substrates. We propose that phosphonocarboxylates prevent only the second GG...
    - 08-jul-2016

  2. Rab27a and Rab27b control different steps of the exosome secretion pathway

    Ostrowski, M.; Carmo, NB.; Krumeich, S.; Fanget, I.; Raposo, G.; Savina, A.; Moita, CF.; Schauer, K.; Hume, AN.; Freitas, RP.; Goud, B.; Benaroch, P.; Hachoen, N.; Fukuda, M.; Desnos, C.; Seabra, MC.; Darchen, F.; Amigorena, S.; Moita, LF.; Thery, C.
    Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b...
    - 08-jul-2016

  3. Effect of the secretory small GTPases Rab27B on breast cancer growth, invasion, and metastasis

    Hendrix, A.; Maynard, D.; Pauwels, P.; Braems, G.; Denys, H.; Van den Broecke, R.; Lambert, J.; Van Belle, S.; Cocquyt, V.; Gespach, C.; Bracke, M.; Seabra, MC.; Gahl, WA.; De Wever, O.; Westbroek, W.
    Methods Expression of green fluorescent protein (GFP) fused with wild-type Rab3D, Rab27A, or Rab27B, or Rab27B point mutants defective in GTP/GDP binding or geranylgeranylation, or transient silencing RNA to the same proteins was used to study Rab27B in estrogen receptor (ER)-positive human breast cancer cell lines (MCF-7, T47D, and ZR75.1). Cell cycle progression was evaluated by flow cytometry, western blotting, and measurement of cell proliferation rates, and invasion was assessed using Matrigel and native type I collagen substrates. Orthotopic tumor growth, local invasion, and metastasis were analyzed in mouse xenograft models. Mass spectrometry identified proinvasive growth regulators that were secreted...
    - 07-jul-2016

  4. Melanosomes at a glance

    Wasmeier, C.; Hume, AN.; Bolasco, G.; Seabra, MC.
    Melanosomes, the pigment granules that provide tissues with colour and photoprotection, are the cellular site of synthesis, storage and transport of melanin pigments. They are synthesised in mammalian skin melanocytes, in choroidal melanocytes and retinal pigment epithelial (RPE) cells in the eye, and in melanophores (a class of pigment-containing cells) in lower vertebrates. The precise fate and functions of melanosomes vary according to cell type – epidermal melanocytes supply neighbouring keratinocytes with melanosomes, which results in the pigmentation of skin and hair, whereas pigment granules are retained intracellularly in RPE cells and choroidal melanocytes. In lower vertebrates, the reversible aggregation...
    - 08-jul-2016

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