The machinery of vesicle fusion

Stanton, Abigail; Hughson, Frederick M.

doi:10.1016/j.ceb.2023.102191

Cited by 16 publications

(9 citation statements)

References 63 publications

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“…Many studies in recent years have suggested that a structural change in the Munc18‐1/syntaxin‐1a complex subsequently occurs, which drives the reaction further. The reaction cascade is quite intricate and the details of this change have been slow to emerge (reviewed in Archbold et al, 2014 ; Baker & Hughson, 2016 ; Jahn & Fasshauer, 2012 ; Rizo, 2022 ; Stanton & Hughson, 2023 ; Südhof & Rothman, 2009 ; Toonen & Verhage, 2003 ; Zhang & Hughson, 2021 ). We have attempted to track down this elusive step in this study.…”

Section: Discussionmentioning

confidence: 99%

“…SNARE proteins form a larger protein family that catalyzes the fusion of various types of transport vesicles in eukaryotic cells. Several other conserved proteins ensure that the SNARE proteins are tightly regulated, including the Rab proteins, Sec1/Munc18‐like (SM) proteins, and a group of tethering proteins known as complex associated with tethering containing helical rods (CATCHR) proteins (Jahn & Fasshauer, 2012 ; Rizo, 2022 ; Stanton & Hughson, 2023 ; Südhof & Rothman, 2009 ; Wang & Ma, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…The fact that two different mutations at different sites of the complex can lead to overall similar effects suggests that syntaxin‐1a remains bound to Munc18‐1 and that a conformational switch within the complex might explain role of Munc18‐1 in promoting SNARE complex assembly (Burkhardt et al, 2008 ; Colbert et al, 2013 ) The idea that SM proteins could guide SNARE complex assembly was suspected early on (Misura et al, 2000 ), but supporting data were slow to come to light (Baker et al, 2015 ; Burkhardt et al, 2008 ). Indeed, it is currently thought that Munc18‐1 catalyzes the formation of a SNARE complex by providing an assembly platform for the three SNARE proteins (Rizo, 2022 ; Stanton & Hughson, 2023 ; Wang & Ma, 2022 ). Slowly, a clearer picture is emerging, but there are still many unanswered questions.…”

Section: Introductionmentioning

confidence: 99%

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Exploring the conformational changes of the Munc18‐1/syntaxin 1a complex

Stefani,

Iwaszkiewicz,

Fasshauer

2024

Protein Science

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Neurotransmitters are released from synaptic vesicles, the membrane of which fuses with the plasma membrane upon calcium influx. This membrane fusion reaction is driven by the formation of a tight complex comprising the plasma membrane SNARE proteins syntaxin‐1a and SNAP‐25 with the vesicle SNARE protein synaptobrevin. The neuronal protein Munc18‐1 forms a stable complex with syntaxin‐1a. Biochemically, syntaxin‐1a cannot escape the tight grip of Munc18‐1, so formation of the SNARE complex is inhibited. However, Munc18‐1 is essential for the release of neurotransmitters in vivo. It has therefore been assumed that Munc18‐1 makes the bound syntaxin‐1a available for SNARE complex formation. Exactly how this occurs is still unclear, but it is assumed that structural rearrangements occur. Here, we used a series of mutations to specifically weaken the complex at different positions in order to induce these rearrangements biochemically. Our approach was guided through sequence and structural analysis and supported by molecular dynamics simulations. Subsequently, we created a homology model showing the complex in an altered conformation. This conformation presumably represents a more open arrangement of syntaxin‐1a that permits the formation of a SNARE complex to be initiated while still bound to Munc18‐1. In the future, research should investigate how this central reaction for neuronal communication is controlled by other proteins.This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploring the conformational changes of the Munc18‐1/syntaxin 1a complex

Stefani,

Iwaszkiewicz,

Fasshauer

2024

Protein Science

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“…First, at the ER-to-Golgi transfer and secondly at the targeting of post-Golgi vesicles or endosomal carriers to the PM. Membrane fusion between cargo carriers and recipient membranes requires specific tethering factors, SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab GTPases, all of which regulate organelle identity as well as the direction of vesicular transport (Cai et al, 2007;Stenmark, 2009;Novick, 2016;Stanton & Hughson, 2023).…”

Section: Introductionmentioning

confidence: 99%

Neosynthesized polarized and non-polarized plasma membrane cargoes follow distinct trafficking routes inAspergillus nidulans

Sagia,

Georgiou,

Chamilos

et al. 2024

Preprint

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Membrane proteins are thought to be sorted to the plasma membrane (PM) via Golgi-dependent trafficking. However, our recent studies in the fungusAspergillus nidulanschallenged the essentiality of Golgi in the biogenesis of non-polarly localized transporters and receptors. Here, we investigate the mechanism of trafficking of membrane proteins, by following the localization of a polar cargo (R-SNARE SynA) versus a non-polar cargo (UapA transporter), synchronously co-expressed in wild-type or isogenic genetic backgrounds repressible for conventional cargo secretion. In wild-type, the two cargoes dynamically label distinct secretory compartments, highlighted by the observation that, unlike SynA, UapA does not colocalize with the late-Golgi. In line with partitioning into distinct early secretory carriers, UapA and SynA translocation to the PM is differentially dependent on Sec13, and importantly the two cargoes collapse in distinct early secretory compartments in a sec31ts mutant or upon CopA repression. Trafficking via distinct cargo-specific carriers is further supported by the observation that repression or inactivation of key proteins essential for late-Golgi /TGN maturation and post-Golgi vesicular secretion did not affect proper trafficking of UapA, but totally blocked SynA secretion. Surprisingly, several specific SNARE proteins that are absolutely essential for conventional cargo vesicular secretion, as well as the exocyst effector RabDSec4, proved dispensable for UapA translocation to the PM. Our findings point to a model where UapA proper trafficking and insertion into the PM might involve non-canonical SNARE combinations. Overall, the present work establishes unequivocally the existence of distinct, cargo-dependent, trafficking mechanisms, initiating at early secretory compartments.

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“…Transport of vesicles to a given destination involves multiple steps, such as the vesicles formation from donor cells, movement of the vesicles, fusion of the vesicles with target membranes and other associated processes (Gerst, 1999 ). Among the proteins involved in this sequence of events, SNAREs (soluble N ‐ethylmaleimide‐sensitive factor attachment protein receptors) are particularly emphasized, as they are necessary for the crucial steps in membrane fusion (Gerst, 1999 ; Stanton & Hughson, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Two distinct SNARE complexes mediate vesicle fusion with the plasma membrane to ensure effective development and pathogenesis of Fusarium oxysporum f. sp. cubense

Fang,

Zhao,

Yang

et al. 2024

Molecular Plant Pathology

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SNAREs (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors) facilitate docking and fusion of vesicles with their target membranes, playing a crucial role in vesicle trafficking and exocytosis. However, the spatial assembly and roles of plasma membrane (PM)‐associated SNAREs in phytopathogen development and pathogenicity are not clearly understood. In this study, we analysed the roles and molecular mechanisms of PM‐associated SNARE complexes in the banana Fusarium wilt fungus Fusarium oxysporum f. sp. cubense tropical race 4 (FocTR4). Our findings demonstrate that FocSso1 is important for the fungal growth, conidiation, host penetration and colonization. Mechanistically, FocSso1 regulates protein secretion by mediating vesicle docking and fusion with the PM and hyphal apex. Interestingly, a FocSso1–FocSec9–FocSnc1 complex was observed to assemble not only at the fungal PM but also on the growing hyphal apex, facilitating exocytosis. FocSso2, a paralogue of FocSso1, was also found to form a ternary SNARE complex with FocSec9 and FocSnc1, but it mainly localizes to the PM in old hyphae. The functional analysis of this protein demonstrated that it is dispensable for the fungal growth but necessary for host penetration and colonization. The other subunits, FocSec9 and FocSnc1, are involved in the fungal development and facilitate host penetration. Furthermore, FocSso1 and FocSnc1 are functionally interdependent, as loss of FocSso1 leads to mis‐sorting and degradation of FocSnc1 in the vacuole and vice versa. Overall, this study provides insight into the formation of two spatially and functionally distinct PM SNARE complexes and their involvement in vesicle exocytosis to regulate development and pathogenicity of FocTR4.

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The machinery of vesicle fusion

Cited by 16 publications

References 63 publications

Exploring the conformational changes of the Munc18‐1/syntaxin 1a complex

Exploring the conformational changes of the Munc18‐1/syntaxin 1a complex

Neosynthesized polarized and non-polarized plasma membrane cargoes follow distinct trafficking routes inAspergillus nidulans

Two distinct SNARE complexes mediate vesicle fusion with the plasma membrane to ensure effective development and pathogenesis of Fusarium oxysporum f. sp. cubense

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