The Vtc proteins in vacuole fusion: coupling NSF activity to V0trans-complex formation

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Abstract
The fusion of cellular membranes comprises several steps; membrane attachment requires priming of SNAREs and tethering factors by Sec18p/NSF (N‐ethylmaleimide sensitive factor) and LMA1. This leads to trans‐SNARE pairing, i.e. formation of SNARE complexes between apposed membranes. The yeast vacuole system has revealed two subsequent molecular events: trans‐complex formation of V‐ATPase proteolipid sectors (V0) and release of LMA1 from the membrane. We have now identified a hetero‐oligomeric membrane integral complex of vacuolar transporter chaperone (Vtc) proteins integrating these events. The Vtc complex associates with the R‐SNARE Nyv1p and with V0. Subunits Vtc1p and Vtc4p control the initial steps of fusion. They are required for Sec18p/NSF activity in SNARE priming, membrane binding of LMA1 and V0trans‐complex formation. In contrast, subunit Vtc3p is required for the latest step, LMA1 release, but dispensible for all preceding steps, including V0trans‐complex formation. This suggests that Vtc3p might act close to or at fusion pore opening. We propose that Vtc proteins may couple ATP‐dependent NSF activity to a subset of V0 sectors in order to activate them for V0trans‐complex formation and/or control fusion pore opening.