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Team Publications
Biogenesis and Functions of Lysosome-Related Organelles
Year of publication 2007
Julia Mallegol, Guillaume Van Niel, Corinne Lebreton, Yves Lepelletier, Céline Candalh, Christophe
Dugave, Joan K Heath, Graça Raposo, Nadine Cerf-Bensussan, Martine Heyman (2007 May 9)
T84-intestinal epithelial exosomes bear MHC class II/peptide complexes
potentiating antigen presentation by dendritic cells.
Gastroenterology : 1866-76
Summary
Intestinal epithelial cells release antigen-presenting vesicles (exosomes) bearing major
histocompatibility complex class II/peptide complexes stimulating specific immune responses
in vivo. To characterize further the role of human epithelial exosomes in antigen
presentation, their capacity to load antigenic peptides, bind immune target cells, and induce
T-cell activation was analyzed in vitro.
Véronique Proux-Gillardeaux, Graça Raposo, Theano Irinopoulou, Thierry Galli (2007 Feb 10)
Expression of the Longin domain of TI-VAMP impairs lysosomal secretion and
epithelial cell migration.
Biology of the cell / under the auspices of the European Cell Biology Organization : 261-71
Summary
TI-VAMP (tetanus neurotoxin-insensitive vesicle-associated membrane protein; also called
VAMP7) belongs to the Longin subfamily of v-SNAREs (vesicular soluble N-ethylmaleimidesensitive fusion protein-attachment protein receptors). The regulatory N-terminal extension,
called the Longin domain, of TI-VAMP has been shown previously to have a dual biochemical
function: it inhibits the capacity of TI-VAMP to form SNARE complexes and it binds to the
delta subunit of the AP-3 (adaptor protein 3) complex in early endosomes, thereby targeting
TI-VAMP to late endosomes.
Mickaël M Ménager, Gaël Ménasché, Maryse Romao, Perrine Knapnougel, Chen-Hsuan Ho,
Mériem Garfa, Graça Raposo, Jérôme Feldmann, Alain Fischer, Geneviève de Saint Basile (2007
Jan 24)
Secretory cytotoxic granule maturation and exocytosis require the effector
protein hMunc13-4.
Nature immunology : 257-67
Summary
Cytotoxic T lymphocytes and natural killer cells exert their cytotoxic activity through the
polarized secretion of cytotoxic granules at the immunological synapse. Rab27a and
hMunc13-4 are critical effectors of the exocytosis of cytotoxic granules. Here we show that
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1
Team Publications
Biogenesis and Functions of Lysosome-Related Organelles
the cytotoxic function of lymphocytes requires the cooperation of two types of organelles:
the lysosomal cytotoxic granule and the endosomal ‘exocytic vesicle’. Independently of
Rab27a, hMunc13-4 mediated the assembly of Rab11(+) recycling and Rab27(+) late
endosomal vesicles, constituting a pool of vesicles destined for regulated exocytosis. It also
primed cytotoxic granule fusion, possibly through interaction with active Rab27a. Cytotoxic T
lymphocyte-target cell recognition induced rapid polarization of both types of organelles,
which coalesced near the cell-cell contact area. Our data provide insight into the regulation
of the generation and release of cytotoxic granules by effector cytotoxic T lymphocytes and
natural killer cells.
Year of publication 2006
Subba Rao Gangi Setty, Danièle Tenza, Steven T Truschel, Evelyn Chou, Elena V Sviderskaya,
Alexander C Theos, M Lynn Lamoreux, Santiago M Di Pietro, Marta Starcevic, Dorothy C Bennett,
Esteban C Dell'Angelica, Graça Raposo, Michael S Marks (2006 Dec 22)
BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes
toward lysosome-related organelles.
Molecular biology of the cell : 768-80
Summary
Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defects in the
formation and function of lysosome-related organelles such as melanosomes. HPS in humans
or mice is caused by mutations in any of 15 genes, five of which encode subunits of
biogenesis of lysosome-related organelles complex (BLOC)-1, a protein complex with no
known function. Here, we show that BLOC-1 functions in selective cargo exit from early
endosomes toward melanosomes. BLOC-1-deficient melanocytes accumulate the
melanosomal protein tyrosinase-related protein-1 (Tyrp1), but not other melanosomal
proteins, in endosomal vacuoles and the cell surface due to failed biosynthetic transit from
early endosomes to melanosomes and consequent increased endocytic flux. The defects are
corrected by restoration of the missing BLOC-1 subunit. Melanocytes from HPS model mice
lacking a different protein complex, BLOC-2, accumulate Tyrp1 in distinct downstream
endosomal intermediates, suggesting that BLOC-1 and BLOC-2 act sequentially in the same
pathway. By contrast, intracellular Tyrp1 is correctly targeted to melanosomes in
melanocytes lacking another HPS-associated protein complex, adaptor protein (AP)-3. The
results indicate that melanosome maturation requires at least two cargo transport pathways
directly from early endosomes to melanosomes, one pathway mediated by AP-3 and one
pathway mediated by BLOC-1 and BLOC-2, that are deficient in several forms of HPS.
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