IHEM   20887
Unidad Ejecutora - UE
congresos y reuniones científicas
Autophagy: Rabs, SNAREs and more.
Otsu, Japón
Simposio; 5th International Symposium on Autophagy; 2009
AUTOPHAGY: RABS, SNARES AND MORE AUTOPHAGY: RABS, SNARES AND MORE María I. Colombo Laboratorio de Biología Celular y Molecular, IHEM-CONICET,  Facultad de Ciencias Médicas, Universidad Nacional de Cuyo – Casilla de Correo 56 - Mendoza, 5500, Argentina. Key words: autophagosomes, multivesicular bodies, fusion machinery, Rabs, SNAREs Despite the remarkable progress achieved in the last few years to elucidate the autophagy pathway at the molecular level very little is known about the fusion machinery involved in the different steps of the autophagic process. Two families of proteins: the small GTPases Rab and the SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), are essential components of the vesicular trafficking system conserved through evolution. The Rab family of small GTPases is one of the largest families with more than 60 members in the human genome. Rab proteins localize in specific intracellular compartments and via the recruitment of effector proteins coordinate sequential steps such as vesicle formation, transport, and tethering and fusion with the target compartment. Once the vesicles are in close proximity the last fusion step is mediated by the formation of the trans-SNARE complexes. It is believed that the specificity and efficiency of the final membrane fusion event is enhanced by the coordinated function of both Rabs and SNAREs. We initially determined that one member of the Rab family, Rab24, localized to autophagic compartments. Although the precise role of this protein remains to be elucidated, new evidence implies its participation in later events. We and others have presented evidence that Rab7 plays an essential role in the autophagic pathway in higher eukaryotic cells. The results indicate that Rab7 is directly involved in fusion with the lysosomes allowing the maturation of autophagosomes. Additional results from our group indicate that other members of the Rab family also participate in specific events of the pathway such as the initial formation of the autophagic vesicle, pointing to the source of the autophagosomal membrane. Using a combination of toxins and truncated SNARE molecules we have also identified in mammalian cells SNARE proteins required for fusion between autophagosomes and the endo/lysosomal compartment. In addition, the role of other components of the fusion machinery such as the AAA-ATPase NSF (N-ethylmaleimide sensitive factor), a chaperone protein whose ATPase activity is required for the disassembly of the SNARE complex after fusion, will be also presented.