IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
32Molecular components involved in autophagy trafficking events.
Autor/es:
COLOMBO, M.I.
Lugar:
Campana, Buenos Aires, Argentina.
Reunión:
Workshop; Exciting Biologies series 2009: Biology in Balance; 2009
Institución organizadora:
Cell Press, Massachusetts General Hospital y Fundación IPSEN
Resumen:
molecular components involved in AUTOPHAGY trafficking events   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.  Maintaining cellular homeostasis is one of the major functions of autophagy. Dispensable or aggregated proteins as well as superfluous or damaged organelles are removed to regulate the composition and size of the cytoplasm. Since autophagy is a constitutive active process the constant removal of useless components and replacement with newly synthesized ones guarantee cellular homeostasis. In the process of macroautophagy, portions of the cytoplasm and organelles are first engulfed by autophagosomes. These structures sequentially fuse with endosomes and finally with lysosomes to degrade and recycle the sequestered components. In order to understand this fundamental process it is essential to determine how this pathway is regulated at the molecular level. To date very little is known about the fusion machinery involved in the different steps of the autophagic process. The small GTPases Rab and the SNAREs, are essential components of vesicular trafficking. Rab proteins localize in specific intracellular compartments coordinating sequential steps such as vesicle formation, transport, and tethering and fusion with the target compartment. The last fusion step is mediated by the formation of the trans-SNARE complexes. We have determined that members of the Rab family, Rab24 and Rab7, localize to autophagic and late endocytic compartments allowing the maturation of autophagosomes. We have evidence that other members of the Rab family also participate in the initial formation of the autophagosomes, pointing to the source of the sequestering 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