Potential role of Rab 21 and VARP in the exocytosis of autophagic vesicles

BARBOSA, CAROLINA; COLOMBO, MARÍA ISABEL; FADER KAISER, CLAUDIO MARCELO

Rosario

Congreso; 50th reunión anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2014

SAIB

Autophagy is a process by which long-live proteins and cellular components are recycled in a lysosomal-based degradation. LC3 is the main protein present in the membrane of autophagic vesicles (autophagosomes). Several signals can trigger autophagy in mammalian cells such as nutrient privation. Recent work has demonstrated that VAMP7 is necessary to deliver ATP-containing autophagosomes to the edge of the cell upon starvation, promoting the exocytosis of this nucleotide. VAMP7 is involved in the traffic from Golgi to plasma membrane, associated with the GTPase Rab21 and its GEF, Varp. The aim of this study was to evaluate the role of the Rab21 and Varp, in the autophagosomes transport to the cell periphery. HeLa cells were cotransfected with plasmids encoding RFP-LC3 and GFP-Rab21, YFP-Rab32 or GFP-VARP. Cells were incubated under starvation conditions or in complete medium in the presence of rapamycin or resveratrol for 4 hours. Our data show that autophagy induction generates an increased number of autophagic structures labeled with Rab21 or Varp localized at the cell periphery. In contrast, Rab32 positive autophagosomes were distributed at the perinuclear region, where colocalized with the lysosomal marker lysotracker. Our results suggest that Rab21 and Varp are vesicular transport proteins that participate in the redistribution of the autophagosomes toward the cell periphery