Frédéric Pincet
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Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release Open
The critical protein Munc13 serves numerous roles in the docking and priming of synaptic vesicles. On the presynaptic plasma membrane, Munc13 is organized into nanoclusters corresponding to release sites where synaptic vesicles dock and fu…
Lithium fine tunes lipid membranes through phospholipid binding Open
Lithium is commonly prescribed for bipolar disorder due to its proven efficacy on patients. Despite this effectiveness, the molecular mechanisms underlying its action remain poorly understood, as it appears to influence numerous unrelated …
Dual-Ring SNAREpin Machinery Tuning for Fast Synaptic Vesicle Fusion Open
During neurotransmission, neurotransmitters are released less than a millisecond after the arrival of the action potential. To achieve this ultra-fast event, the synaptic vesicle must be pre-docked to the plasma membrane. In this primed st…
Photosensitive Nanoprobes for Rapid High Purity Isolation and Size‐Specific Enrichment of Synthetic and Extracellular Vesicle Subpopulations Open
The biggest challenge in current isolation methods for lipid bilayer‐encapsulated vesicles, such as exosomes, secretory, and synthetic vesicles, lies in the absence of a unified approach that seamlessly delivers high purity, yield, and sca…
Long-Lived Planar Asymmetric Suspended Membranes for Investigating Protein Dynamics and Membrane Fusion Open
Membrane fusion is pivotal in cellular signaling and trafficking, requiring an intricate understanding of the interactions between proteins and lipids. Addressing the limitations of studying complex protein dynamics in cellular environment…
A model for collagen secretion by intercompartmental continuities Open
Newly synthesized secretory proteins are exported from the endoplasmic reticulum (ER) at specialized subcompartments called exit sites (ERES). Cargoes like procollagen are too large for export by the standard COPII-coated vesicle of 60 nm …
Membrane Tubulation with a Biomembrane Force Probe Open
Tubulation is a common cellular process involving the formation of membrane tubes ranging from 50 nm to 1 µm in diameter. These tubes facilitate intercompartmental connections, material transport within cells and content exchange between c…
View article: Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle Open
The synaptic vesicle protein Synaptophysin (Syp) has long been known to form a complex with the Vesicle associated soluble N-ethylmaleimide sensitive fusion protein attachment receptor (v-SNARE) Vesicle associated membrane protein (VAMP), …
View article: Diacylglycerol-dependent hexamers of the SNARE-assembling chaperone Munc13-1 cooperatively bind vesicles
Diacylglycerol-dependent hexamers of the SNARE-assembling chaperone Munc13-1 cooperatively bind vesicles Open
Munc13-1 is essential for vesicle docking and fusion at the active zone of synapses. Here, we report that Munc13-1 self-assembles into molecular clusters within diacylglycerol-rich microdomains present in phospholipid bilayers. Although th…
A model for collagen secretion by intercompartmental continuities Open
Newly synthesized secretory proteins are exported from endoplasmic reticulum (ER) at specialized subcompartments called exit sites (ERES). Cargoes like procollagen are too large for export by the standard COPII-coated vesicle of 60 nm aver…
View article: Turbocharging synaptic transmission
Turbocharging synaptic transmission Open
Evidence from biochemistry, genetics, and electron microscopy strongly supports the idea that a ring of Synaptotagmin is central to the clamping and release of synaptic vesicles (SVs) for synchronous neurotransmission. Recent direct measur…
View article: Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release
Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release Open
The critical presynaptic protein Munc13 serves numerous roles in the process of docking and priming synaptic vesicles. Here we investigate the functional significance of two distinct oligomers of the Munc13 core domain (Munc13C) comprising…
View article: Synaptophysin Chaperones the Assembly of 12 SNAREpins under each Ready-Release Vesicle
Synaptophysin Chaperones the Assembly of 12 SNAREpins under each Ready-Release Vesicle Open
The synaptic vesicle protein Synaptophysin has long been known to form a complex with the v-SNARE VAMP, but a more specific molecular function or mechanism of action in exocytosis has been lacking because gene knockouts have minimal effect…
View article: Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer
Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer Open
Hierarchical organization of integral membrane proteins (IMP) and lipids at the membrane is essential for regulating myriad downstream signaling. A quantitative understanding of these processes requires both detections of oligomeric organi…
Actuating tension-loaded DNA clamps drives membrane tubulation Open
Membrane dynamics in living organisms can arise from proteins adhering to, assembling on, and exerting force on cell membranes. Programmable synthetic materials, such as self-assembled DNA nanostructures, offer the capability to drive memb…
The beginning and the end of <span>SNARE</span>‐induced membrane fusion Open
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 ne…
Editor's evaluation: All-atom molecular dynamics simulations of Synaptotagmin-SNARE-complexin complexes bridging a vesicle and a flat lipid bilayer Open
Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Methods Data availability References Decision letter Author response Article and author information Metrics Abstract Synaptic vesicles are primed into a …
Cooperation of Conical and Polyunsaturated Lipids to Regulate Initiation and Processing of Membrane Fusion Open
The shape of lipids has long been suspected to be a critical determinant for the control of membrane fusion. To experimentally test this assertion, we used conical and malleable lipids and measured their influence on the fusion kinetics. W…
View article: Vesicle capture by membrane‐bound Munc13‐1 requires self‐assembly into discrete clusters
Vesicle capture by membrane‐bound Munc13‐1 requires self‐assembly into discrete clusters Open
Munc13‐1 is a large banana‐shaped soluble protein that is involved in the regulation of synaptic vesicle docking and fusion. Recent studies suggest that multiple copies of Munc13‐1 form nano‐assemblies in active zones of neurons. However, …
View article: Nascent fusion pore opening monitored at single-SNAREpin resolution
Nascent fusion pore opening monitored at single-SNAREpin resolution Open
Significance Using our recently designed microfluidic setup, we investigated the early stage of SNAREpin-induced fusion. We discovered the existence of subsecond transient fusion pores with a well-defined subnanometer size that occur when …
View article: Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly
Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly Open
Synaptic vesicle fusion is mediated by SNARE proteins—VAMP2 on the vesicle and Syntaxin‐1/SNAP25 on the presynaptic membrane. Chaperones Munc18‐1 and Munc13‐1 cooperatively catalyze SNARE assembly via an intermediate ‘template’ complex con…