The beginning and the end of SNARE‐induced membrane fusion

Abstract

Membrane fusion is not a spontaneous process. Physiologically, the formation of coiled-coil protein complexes, the SNAREpins, bridges the membrane of a vesicle and a target membrane, brings them in close contact and provides the energy necessary for their fusion. In this review, we utilize results from in vitro experiments and simple physics and chemistry models to dissect the kinetics and energetics of the fusion process from the encounter of the two membranes to the full expansion of a fusion pore. We find three main energy barriers that oppose the fusion process: SNAREpin initiation, fusion pore opening and expansion. SNAREpin initiation is inherent to the proteins and makes in vitro fusion kinetics experiments rather slow. The kinetics are physiologically accelerated by effectors. The energy barriers that precede pore opening and pore expansion can be overcome by several SNAREpin acting in concert.

Apolipoproteins L1 and L3 control mitochondrial membrane dynamics

“…SNARE-mediated membrane fusion requires coiling of four helices (SNARE domains) located near transmembrane domains. 88 , 89 We investigated the possible interaction of VAMP8 with different APOL3 helices with coiling potential ( Figure S6 C), including the “membrane-addressing domain” (MAD), 13 a double-stranded helix (MAD1-2) near the transmembrane hairpin. APOL3 interaction with VAMP8 was not driven by LZs because either LZ2 deletion or mutation of key LZ1 leucines conserved full APOL3 interaction with either sVAMP8 or TbVAMP7B peptides ( Figure 6 D).…”

α-Synuclein is required for sperm exocytosis at a post-fusion stage

“…Despite similar molecular machineries, exocytosis proceeds at different speeds, being much faster in synaptic vesicles (∼40 nm diameter, high curvature) than in chromaffin and insulin granules (∼100–300 nm diameter, low curvature) ( Kreutzberger et al, 2019 ). The fusion pore that opens between the fusing membranes and connects the granule’s lumen with the extracellular space can evolve in various ways: it can dilate—slowly or rapidly—to allow full cargo release (full fusion), it can reseal (kiss and run) or open and close repeatedly (flickering) ( Karatekin, 2018 ; Mion et al, 2022 ). Among other factors, pore dynamics, vesicle size and curvature of the membrane determine the kinetics of cargo release.…”

Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release

“…An additional advantage of sequestering a small number of SNARE proteins into a highly confined and organized arrangement is a dramatic acceleration of SNARE assembly speed compared to an unorganized diffusion-limited alternative 44 . The TIRF SNAREpin counting experiments presented here indicate that six SNAREpins are assembled in less than 100 msec upon vesicle docking, consistent with the observed rapid replenishment of synaptic release sites during activity that have an estimated time interval of 250 msec at the calyx of Held 45 .…”