Dynamin−SNARE interactions control trans-SNARE formation in intracellular membrane fusion

Alpadi, Kannan; Kulkarni, Aditya; Namjoshi, Sarita; Srinivasan, Sankaranarayanan; Sippel, Katherine H.; Ayscough, Kathryn R.; Zieger, Martin; Schmidt, Andrea; Mayer, Andreas; Evangelista, Michael A.; Peters, Christopher M.

doi:10.1038/ncomms2724

Cited by 30 publications

(34 citation statements)

References 32 publications

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“…We also confirm that these stimuli have the opposing effect on homotypic vacuole fusion, lending additional support to the idea that fission and fusion are highly coordinated (e.g. Alpadi et al, 2013). This is a requirement for efficient changes in morphology, whereby if fission occurs, the counteracting process of fusion must be blocked for the organelle to remain fragmented, i.e.…”

supporting

confidence: 61%

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Acetate and hypertonic stress stimulate organelle membrane fission using distinct phosphatidylinositol signals

Patel¹,

Cl²

2018

Preprint

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Running Title Vacuole morphology control by Rab and PI signalingFor social media (@drbrettphd) Organelle morphology reflects a balance between fission and fusion. Using the yeast vacuole as a model, Patel and Brett use a new in vitro fission assay to further resolve the molecular circuitry that underlies these opposing processes. KeywordsMembrane fission, membrane fusion, organelle morphology, yeast vacuole, phosphatidylinositol . CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/398685 doi: bioRxiv preprint first posted online Aug. 23, 2018;Patel & Brett, page 2 ABSTRACT Organelle morphology reflects an equilibrium between membrane fusion and fission that determines size, shape and copy number. By studying the yeast vacuole as a model, the conserved molecular mechanisms responsible for organelle fusion have been revealed. 5However, a detailed understanding of vacuole fission and how these opposing processes respond to the cell cycle, osmoregulation or metabolism to change morphology remain elusive.Thus, herein we describe a new fluorometric assay to measure vacuole fission in vitro. For proof-of-concept, we use this assay to confirm that acetate, a key intermediary metabolite, triggers vacuole fission in vitro and show that it also blocks homotypic vacuole fusion. The basis 10 of this effect is distinct from hypertonic stress, a known trigger of fission and inhibitor of fusion that inactivates the Rab-GTPase Ypt7: Treatment with the phosphatidylinositol-kinase inhibitor wortmannin or the catalytic domain of the Rab-GAP (GTPase Activating Protein) Gyp1 reveal that fission can be triggered by Ypt7 inactivation alone in absence of hypertonic stress, placing it upstream of PI-3,5-P2 synthesis and osmosis required for membrane scission. Whereas acetate 15 seems to block PI-4-kinase to possibly increase the pool of PI on vacuole membranes needed to synthesize sufficient PI-3,5-P2 for fission. Thus, we speculate that both PI-4-P and PI-3-P arms of PI-P signaling drive changes in membrane fission and fusion responsible altering vacuole morphology in response to cellular metabolism or osmoregulation.

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confidence: 61%

“…These findings have led to the idea that the 30 underlying machinery is highly integrated (e.g. LaGrassa and Ungermann, 2005;Alpadi et al, 2013). The basis of homotypic vacuole fusion has been resolved with incredible molecular precision (see Wickner, 2010).…”

Section: Introductionmentioning

confidence: 99%

Acetate and hypertonic stress stimulate organelle membrane fission using distinct phosphatidylinositol signals

Patel¹,

Cl²

2018

Preprint

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“…6F) (Thorngren et al, 2004). Whether the observed requirement of Vps1 for membrane fusion (Alpadi et al, 2013;Kulkarni et al, 2014;Peters et al, 2004) relates to either a fusion-specific function or rather to a consequence of a defect in recycling, needs further investigation. Our data show that the fusion defect applies to both retromer and vps1 mutants, even though the fusion machinery is apparently present on vacuoles.…”

Section: Discussionmentioning

confidence: 99%

“…Vps1 has been previously linked to vacuole biogenesis and was shown to affect not only vacuole fission but also fusion (Alpadi et al, 2013;Peters et al, 2004). The vps1D mutant has a defect in in vitro vacuole fusion, and recombinant Vps1 interacts with the SNARE Vam3 (Peters et al, 2004).…”

Section: The Retromer and Vps1 Affect Vacuole Homeostasismentioning

confidence: 99%

Retromer and the dynamin Vps1 cooperate in the retrieval of transmembrane proteins from vacuoles

Arlt

Reggiori

Ungermann

2014

Journal of Cell Science

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Endosomes are dynamic organelles that need to combine the ability to successfully deliver proteins and lipids to the lysosome-like vacuole, and recycle others to the Golgi or the plasma membrane. We now show that retromer, which is implicated in retrieval of proteins from endosomes to the Golgi or to the plasma membrane, can act on vacuoles. We explore its function using an assay that allows us to dissect the required cofactors during recycling. We demonstrate that recycling of the transmembrane receptor Vps10 from vacuoles requires the retromer, the dynamin-like Vps1, and the Rab7 GTPase Ypt7. Retromer and Vps1 leave the vacuole together with the cargo, whereas Ypt7 stays behind, in agreement with its regulatory function. Recycled cargo then accumulates at endosomes and later at the Golgi, implying consecutive sorting steps to the final destination. Our data further suggest that retromer and Vps1 are essential to maintain vacuole membrane organization. Taken together, our data demonstrate that retromer can cooperate with Vps1 and the Rab Ypt7 to clear the vacuole of selected membrane proteins.

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“…In yeast, the dynamin homolog Vps1p interacts with the t-SNARE Vamp3; the disruption of this association with an antibody against Vps1p inhibits the fusion reaction (82). More recently, Peters’ lab has demonstrated that Vps1 binds to the Qa SNARE Vamp3 and controls trans-SNARE formation, which is essential for membrane fusion in yeasts (83). …”

Section: Dynamin As a Facilitator Of Membrane Fusionmentioning

confidence: 99%

Dynamin-2 Function and Dysfunction Along the Secretory Pathway

González‐Jamett¹,

Momboisse²,

Haro-Acuña³

et al. 2013

Front. Endocrinol.

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Dynamin-2 is a ubiquitously expressed mechano-GTPase involved in different stages of the secretory pathway. Its most well-known function relates to the scission of nascent vesicles from the plasma membrane during endocytosis; however, it also participates in the formation of new vesicles from the Golgi network, vesicle trafficking, fusion processes and in the regulation of microtubule, and actin cytoskeleton dynamics. Over the last 8 years, more than 20 mutations in the dynamin-2 gene have been associated to two hereditary neuromuscular disorders: Charcot–Marie–Tooth neuropathy and centronuclear myopathy. Most of these mutations are grouped in the pleckstrin homology domain; however, there are no common mutations associated with both disorders, suggesting that they differently impact on dynamin-2 function in diverse tissues. In this review, we discuss the impact of these disease-related mutations on dynamin-2 function during vesicle trafficking and endocytotic processes.

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Dynamin−SNARE interactions control trans-SNARE formation in intracellular membrane fusion

Cited by 30 publications

References 32 publications

Acetate and hypertonic stress stimulate organelle membrane fission using distinct phosphatidylinositol signals

Acetate and hypertonic stress stimulate organelle membrane fission using distinct phosphatidylinositol signals

Retromer and the dynamin Vps1 cooperate in the retrieval of transmembrane proteins from vacuoles

Dynamin-2 Function and Dysfunction Along the Secretory Pathway

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