TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways.
During reticulocyte maturation, some membrane proteins and organelles that are not required in the mature red cell are lost. Several of these proteins are released into the extracellular medium associated with the internal vesicles present in multivesicular bodies (MVBs). Likewise, organelles such as mitochondria and endoplasmic reticulum are wrapped into double membrane vacuoles (i.e., autophagosomes) and degraded via autophagy. Morphological, molecular, and biochemical studies have shown that autophagosomes fuse with MVBs forming the so-called amphisomes, a prelysosomal hybrid organelle. SNAREs are key molecules of the vesicle fusion machinery. TI-VAMP/VAMP7 and VAMP3/cellubrevin are two v-SNARE proteins involved in the endocytic and exocytic pathways. We have previously shown that in the human leukemic K562 cells, Rab11 decorates MVBs and it is necessary for fusion between autophagosomes with MVBs. In the present report, we present evidence indicating that VAMP3 is required for the fusion between MVBs with autophagosomes to generate the amphisome, allowing the maturation of the autophagosome, but it does not seem to be involved in the next step, i. e., fusion with the lysosome. On the other hand, we demonstrate that VAMP7 is necessary for this latter event, allowing the completion of the autophagic pathway. Furthermore, VAMP7 and ATPase NSF, a protein required for SNAREs disassembly, participate in the fusion between MVBs with the plasma membrane to release the internal vesicles (i.e., exosomes) into the extracellular medium.
Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología (IHEM)-CONICET, Universidad Nacional de Cuyo, Casilla de Correo 56, Centro Universitario, Parque General San Martín, (5500) Mendoza, Argentina.
Claudio Marcelo
CM
Fader
Diego Germán
DG
Sánchez
María Belén
MB
Mestre
María Isabel
MI
Colombo
D001343:Autophagy / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D008247:Lysosomes / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology*; D057146:Multivesicular Bodies / Q000378:metabolism*; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism; D050683:R-SNARE Proteins / Q000378:metabolism*; D051040:Vesicle-Associated Membrane Protein 3 / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D052066:N-Ethylmaleimide-Sensitive Proteins; D050683:R-SNARE Proteins; D051040:Vesicle-Associated Membrane Protein 3; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C494946:VAMP3 protein, human; C121241:VAMP7 protein, human