Btn3 regulates the endosomal sorting function of the yeast Ent3 epsin, an adaptor for SNARE proteins

Ent3 and Ent5 are yeast epsin N-terminal homology (ENTH) domain-containing proteins involved in protein trafficking between the Golgi and late endosomes. They interact with clathrin, clathrin adaptors at the Golgi (AP-1 and GGA) and different SNAREs (Vti1, Snc1, Pep12 and Syn8) required for vesicular transport at the Golgi and endosomes. To better understand the role of these epsins in membrane trafficking, we performed a protein-protein interaction screen. We identified Btn3 (also known as Tda3), a putative oxidoreductase, as a new partner of both Ent3 and Ent5. Btn3 is a negative regulator of the Batten-disease-linked protein Btn2 involved in the retrieval of specific SNAREs (Vti1, Snc1, Tlg1 and Tlg2) from the late endosome to the Golgi. We show that Btn3 endosomal localization depends on the epsins Ent3 and Ent5. We demonstrated that in btn3Delta mutant cells, endosomal sorting of ubiquitylated cargos and endosomal recycling of the Snc1 SNARE are delayed. We thus propose that Btn3 regulates the sorting function of two adaptors for SNARE proteins, the epsin Ent3 and the Batten-disease-linked protein Btn2

Discovery and progress in our understanding of the regulated secretory pathway in neuroendocrine cells

In this review we start with a historical perspective beginning with the early morphological work done almost 50 years ago. The importance of these pioneering studies is underscored by our brief summary of the key questions addressed by subsequent research into the mechanism of secretion. We then highlight important advances in our understanding of the formation and maturation of neuroendocrine secretory granules, first using in vitro reconstitution systems, then most recently biochemical approaches, and finally genetic manipulations in vitro and in vivo

Arfaptine-1 et biogenèse des granules de sécrétion

International audienceNo abstract availabl

Btn3 regulates the endosomal sorting function of the yeast Ent3 epsin, an adaptor for SNARE proteins

International audienceEnt3 and Ent5 are yeast epsin N-terminal homology (ENTH) domain-containing proteins involved in protein trafficking between the Golgi and late endosomes. They interact with clathrin, clathrin adaptors at the Golgi (AP-1 and GGA) and different SNAREs (Vti1, Snc1, Pep12 and Syn8) required for vesicular transport at the Golgi and endosomes. To better understand the role of these epsins in membrane trafficking, we performed a protein–protein interaction screen. We identified Btn3 (also known as Tda3), a putative oxidoreductase, as a new partner of both Ent3 and Ent5. Btn3 is a negative regulator of the Batten-disease-linked protein Btn2 involved in the retrieval of specific SNAREs (Vti1, Snc1, Tlg1 and Tlg2) from the late endosome to the Golgi. We show that Btn3 endosomal localization depends on the epsins Ent3 and Ent5. We demonstrated that in btn3D mutant cells, endosomal sorting of ubiquitylated cargos and endosomal recycling of the Snc1 SNARE are delayed. We thus propose that Btn3 regulates the sorting function of two adaptors for SNARE proteins, the epsin Ent3 and the Batten-disease-linked protein Btn2

First enantioselective total synthesis and configurational assignments of suberosenone and suberosanone as potential antitumor agents

International audienceThe first enantioselective total syntheses of two marine sesquiterpenes (1R)-suberosenone and (1R)-suberosanone are achieved leading to revision of the AC of natural (1S)-suberosanone. Key elements of the synthesis include hyperbaric asymmetric Michael addition and highly efficient silver trifluoroacetate mediated α-alkylation for the formation of ring A

The BAR Domain Protein Arfaptin-1 Controls Secretory Granule Biogenesis at the trans-Golgi Network

International audienceBAR domains can prevent membrane fission through their ability to shield necks of budding vesicles from fission-inducing factors. However, the physiological role of this inhibitory function and its regulation is unknown. Here we identify a checkpoint involving the BAR-domain-containing protein Arfaptin-1 that controls biogenesis of secretory granules at the trans-Golgi network (TGN). We demonstrate that protein kinase D (PKD) phosphorylates Arfaptin-1 at serine 132, which disrupts the ability of Arfaptin-1 to inhibit the activity of ADP ribosylation factor, an important component of the vesicle scission machinery. The physiological significance of this regulatory mechanism is evidenced by loss of glucose-stimulated insulin secretion due to granule scission defects in pancreatic β cells expressing nonphosphorylatable Arfaptin-1. Accordingly, depletion of Arfaptin-1 leads to the generation of small nonfunctional secretory granules. Hence, PKD-mediated Arfaptin-1 phosphorylation is necessary to ensure biogenesis of functional transport carriers at the TGN in regulated secretion

L’homme présupposé

Les philosophies et les sciences humaines sont des fabriques de l’homme, selon le double sens du génitif. Elles sont fabriquées par des hommes, mais elles fabriquent aussi l’homme, en tant qu’elles véhiculent une représentation de ce qui le constitue et (ou) du rapport qu’il entretient avec ce qui n’est pas lui (nature, société). La construction d’un discours impose en effet une grille de lecture, un découpage et une articulation du réel. Aussi, en dépit de l’effort que l’on rencontre parfois pour élaborer des discours sans présupposé ontologique sur la nature humaine, une prise de position au sujet de l’homme semble en fait inévitable. Prendre par exemple pour point de vue celui de l’individu ou, au contraire, celui du tout social n’est pas neutre mais il s’agit déjà d’une façon de régler le rapport de l’un à l’autre. Et partir d’un homme ramené au statut d’agent rationnel visant à maximiser son profit est un choix massif qu’il convient d’analyser. Mais, s’il y a toujours, en philosophie morale et politique, ou dans les sciences humaines, des présupposés anthropologiques, on ne trouve pas forcément dans, ou à l’arrière-plan de tout discours sur les hommes, l’admission d’une essence générique de l’homme ; autrement dit, le présupposé peut être aussi de contestation. Quoi qu’il en soit, il faut mettre en évidence un personnage abstrait, parfois assumé, parfois caché et parfois contesté donc, mais toujours là à sa façon, à défaut d’être à chaque fois opératoire