Dynamin in fission and fusion

Abstract

The same GTPase that tears membranes apart is needed to put them back together, based on results from Christopher Peters, Andreas Mayer, and colleagues (Universite de Lausanne, Switzerland). The dual regulation may ensure that only one of the two competing processes goes on at any one time. Figure Without dynamin, yeast vacuoles have both fission and fusion failures. The Swiss group finds that yeast cells lacking the dynamin homologue Vps1p resemble both fission and fusion mutants. The effects were seen in the morphology of the vacuoles, where Vps1p was localized. Some cells had a single enlarged vacuole, whereas others had many small vacuolar fragments. The two phenotypes were seen because Vps1p functions in both pathways. As expected given dynamin's known fission activity, vacuole fragmentation in response to salt stress was disrupted in the mutant. But vacuole fusion reactions also required Vps1p, which was found to interact with the Vam3p t-SNARE. Vps1p recruited the t-SNARE into large membrane complexes containing multiple copies of both proteins. This organization favors fragmentation, since dynamin polymers are the fission-active form. At the same time, fusion was inhibited until Vps1p was released from the vacuole membrane, suggesting that the Vps1p-bound t-SNARE is inactive. The release of Vps1p was controlled by the t-SNARE and its ATPase chaperone, NSF. How NSF is regulated to support or limit fission remains to be addressed. The linking of dynamin with the fusion machinery may prevent repeated futile cycles of fission and fusion. “Intuitively, [this counter-regulation] makes sense,” says Mayer. “When a vesicle is pinched off, SNAREs must be incorporated to make it fusogenic for future reactions. So why are they not active while pinching is going on?” Silencing the t-SNAREs at the site of fission by dynamin's intervention is one way to solve this problem. As vps1 mutants were deficient in vacuole fusion, dynamin must also somehow promote fusion, perhaps by organizing cooperative t-SNARE complexes. Dynamin release from the vacuole might also induce necessary conformational changes in the t-SNARE. Reference: Peters, C., et al. 2004. Cell. 119:667–678. [PubMed]