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Massimo D'Agostino, Ph.D. - "Non-expanding fusion pores are a stable intermediate of vacuole membrane fusion in vivo"

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università' Federico II, Napoli
When Mar 13, 2018
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Abstract
While fusion of secretory vesicles in regulated exocytosis is restrained by accessory proteins, fusion of all other intracellular membranes is believed to be constitutive and rapid. SNAREs drive these membranes through docking, hemifusion, fusion pore formation and final pore expansion. Theory predicts that fusion pore expansion faces a major energy barrier but corresponding states with stable, non-opening pores have remained elusive in vivo. Here, we show that docked yeast vacuoles exchange lipids from both of their membrane leaflets, but they do not mix lumenal content. This suggests the existence of a nanoscopic fusion pore. The pore is located close to the vertex ring of fusion proteins that surrounds the organelle-organelle contact zone. Full vacuole fusion can be induced by osmotic pressure gradients, but only after a nanoscopic pore had been established through vacuolar SNAREs and the SM-protein containing HOPS complex. The nanoscopic, metastable fusion pore may thus allow vacuoles to rapidly adapt organelle volume to increases in content. Such pores are then not only a transient intermediate but can be a long-lived, physiologically relevant and regulated state of SNARE-dependent membrane fusion.

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