Mécanismes moléculaires du transport intracellulaire

Publications de l’équipe

Année de publication : 2003

Ragna Sannerud, Jaakko Saraste, Bruno Goud (2003 Aug 2)

Retrograde traffic in the biosynthetic-secretory route: pathways and machinery.

Current opinion in cell biology : 438-45 En savoir plus
Résumé

In the secretory pathway, the forward (anterograde) membrane flow is compensated by retrograde transport of proteins and lipids. Membrane recycling is required for the maintenance of organelle homeostasis and the re-use of components of the transport machineries for the generation of new transport intermediates. However, the molecular mechanisms and other cellular functions of retrograde traffic are still poorly understood. In recent years, a multitude of protein factors that function in the secretory pathway have been discovered, most of them originally suggested to play a role in forward trafficking. However, in many cases subsequent studies have revealed that these proteins participate (also) in retrograde traffic. It is likely that this shift will continue, reflecting the fact that the two pathways are intimately connected.

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Sophie Chantalat, Régis Courbeyrette, Francesca Senic-Matuglia, Catherine L Jackson, Bruno Goud, Anne Peyroche (2003 Jun 17)

A novel Golgi membrane protein is a partner of the ARF exchange factors Gea1p and Gea2p.

Molecular biology of the cell : 2357-71 En savoir plus
Résumé

The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserved regulators of membrane dynamics and protein trafficking. The interactions of large ARF GEFs with cellular membranes for localization and/or activation are likely to participate in regulated recruitment of ARF and effectors. However, these interactions remain largely unknown. Here we characterize Gmh1p, the first Golgi transmembrane-domain partner of any of the high-molecular-weight ARF-GEFs. Gmh1p is an evolutionarily conserved protein. We demonstrate molecular interaction between the yeast Gmh1p and the large ARF-GEFs Gea1p and Gea2p. This interaction involves a domain of Gea1p and Gea2p that is conserved in the eukaryotic orthologues of the Gea proteins. A single mutation in a conserved amino acid residue of this domain is sufficient to abrogate the interaction, whereas the overexpression of Gmh1p can compensate in vivo defects caused by mutations in this domain. We show that Gmh1p is an integral membrane protein that localizes to the early Golgi in yeast and in human HeLa cells and cycles through the ER. Hence, we propose that Gmh1p acts as a positive Golgi-membrane partner for Gea function. These results are of general interest given the evolutionary conservation of both ARF-GEFs and the Gmh proteins.

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Dan Lipsker, Umit Ziylan, Ray McDermott, Danièle Spehner, Fabienne Proamer, Jean-Pierre Cazenave, Bruno Goud, Henri de la Salle, Jean Salamero, Daniel Hanau (2003 Feb 27)

Cored tubules are present in human epidermal Langerhans cells.

The Journal of investigative dermatology : 407-10 En savoir plus
Résumé

Cored tubules are ultrastructural organelles described to date only in murine cells belonging to the Langerhans cell family and located in the dermis and its draining lymph nodes. These organelles, the function of which is unknown, differ from Birbeck granules and are interestingly not found in murine epidermal Langerhans cells. In this work we demonstrate that cored tubules are present in freshly isolated human epidermal Langerhans cells. The tubules were found to be interconnected with structures known to belong to the early endosomal pathway and could be immunolabeled with gold-conjugated anti-CD1a and anti-Langerin monoclonal antibodies, but only at 37 degrees C. At this temperature such antibodies are able to progress from the early sorting endosomes to the early recycling endosomes, which in human Langerhans cells include the Birbeck granules. These findings strongly suggest that cored tubules form part of the early recycling compartment.

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Année de publication : 2002

Theodoros Matanis, Anna Akhmanova, Phebe Wulf, Elaine Del Nery, Thomas Weide, Tatiana Stepanova, Niels Galjart, Frank Grosveld, Bruno Goud, Chris I De Zeeuw, Angelika Barnekow, Casper C Hoogenraad (2002 Nov 26)

Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex.

Nature cell biology : 986-92 En savoir plus
Résumé

The small GTPase Rab6a is involved in the regulation of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER) in a coat complex coatomer protein I (COPI)-independent pathway. Here, we used a yeast two-hybrid approach to identify binding partners of Rab6a. In particular, we identified the dynein-dynactin-binding protein Bicaudal-D1 (BICD1), one of the two mammalian homologues of Drosophila Bicaudal-D. BICD1 and BICD2 colocalize with Rab6a on the trans-Golgi network (TGN) and on cytoplasmic vesicles, and associate with Golgi membranes in a Rab6-dependent manner. Overexpression of BICD1 enhances the recruitment of dynein-dynactin to Rab6a-containing vesicles. Conversely, overexpression of the carboxy-terminal domain of BICD, which can interact with Rab6a but not with cytoplasmic dynein, inhibits microtubule minus-end-directed movement of green fluorescent protein (GFP)-Rab6a vesicles and induces an accumulation of Rab6a and COPI-independent ER cargo in peripheral structures. These data suggest that coordinated action between Rab6a, BICD and the dynein-dynactin complex controls COPI-independent Golgi-ER transport.

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Florence Béranger, Alain Mangé, Bruno Goud, Sylvain Lehmann (2002 Aug 7)

Stimulation of PrP(C) retrograde transport toward the endoplasmic reticulum increases accumulation of PrP(Sc) in prion-infected cells.

The Journal of biological chemistry : 38972-7 En savoir plus
Résumé

Prion diseases are fatal and transmissible neurodegenerative disorders characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrP(C)) denoted PrP(Sc). To identify intracellular organelles involved in PrP(Sc) formation, we studied the role of the Ras-related GTP-binding proteins Rab4 and Rab6a in intracellular trafficking of the prion protein and production of PrP(Sc). When a dominant-negative Rab4 mutant or a constitutively active GTP-bound Rab6a protein was overexpressed in prion-infected neuroblastoma N2a cells, there was a marked increase of PrP(Sc) formation. By immunofluorescence and cell fractionation studies, we have shown that expression of Rab6a-GTP delocalizes PrP within intracellular compartments, leading to an accumulation in the endoplasmic reticulum. These results suggest that prion protein can be subjected to retrograde transport toward the endoplasmic reticulum and that this compartment may play a significant role in PrP(Sc) conversion.

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Bruno Goud (2002 Apr 11)

How Rab proteins link motors to membranes.

Nature cell biology : E77-8 En savoir plus
Résumé

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Andrew J Lindsay, Alan G Hendrick, Giuseppina Cantalupo, Francesca Senic-Matuglia, Bruno Goud, Cecilia Bucci, Mary W McCaffrey (2002 Jan 12)

Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein.

The Journal of biological chemistry : 12190-9 En savoir plus
Résumé

Rab4 and Rab11 are small GTPases belonging to the Ras superfamily. They both function as regulators along the receptor recycling pathway. We have identified a novel 80-kDa protein that interacts specifically with the GTP-bound conformation of Rab4, and subsequent work has shown that it also interacts strongly with Rab11. We name this protein Rab coupling protein (RCP). RCP is predominantly membrane-bound and is expressed in all cell lines and tissues tested. It colocalizes with early endosomal markers including Rab4 and Rab11 as well as with the transferrin receptor. Overexpression of the carboxyl-terminal region of RCP, which contains the Rab4- and Rab11-interacting domain, results in a dramatic tubulation of the transferrin compartment. Furthermore, expression of this mutant causes a significant reduction in endosomal recycling without affecting ligand uptake or degradation in quantitative assays. RCP is a homologue of Rip11 and therefore belongs to the recently described Rab11-FIP family.

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