James E. Rothman
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View article: The Golgi Rim is a Precise Tetraplex of Golgin Proteins that Can Self-Assemble into Filamentous Bands
The Golgi Rim is a Precise Tetraplex of Golgin Proteins that Can Self-Assemble into Filamentous Bands Open
Golgin proteins have long been suspected to be organizers of the Golgi stack. Using three-dimensional super-resolution microscopy, we comprehensively localize the human golgin family at the rim of the Golgi apparatus at 10-20 nm resolution…
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…
View article: Starting at Go: Protein structure prediction succumbs to machine learning
Starting at Go: Protein structure prediction succumbs to machine learning Open
This year’s Albert Lasker Basic Medical Research Award recognizes the invention of AlphaFold, a revolutionary advance in the history of protein research which for the first time offers the practical ability to accurately predict the three-…
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: Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery
Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery Open
Here, we introduce the full functional reconstitution of genetically validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, and Complexin) for synaptic vesicle priming and release in a geometry that enables detailed chara…
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: Novel Roles for Diacylglycerol in Synaptic Vesicle Priming and Release Revealed by Complete Reconstitution of Core Protein Machinery
Novel Roles for Diacylglycerol in Synaptic Vesicle Priming and Release Revealed by Complete Reconstitution of Core Protein Machinery Open
Here we introduce the full functional reconstitution of genetically-validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, Complexin) for synaptic vesicle priming and release in a geometry that enables detailed characteri…
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…
View article: Synaptotagmin rings as high-sensitivity regulators of synaptic vesicle docking and fusion
Synaptotagmin rings as high-sensitivity regulators of synaptic vesicle docking and fusion Open
Synchronous release at neuronal synapses is accomplished by a machinery that senses calcium influx and fuses the synaptic vesicle and plasma membranes to release neurotransmitters. Previous studies suggested the calcium sensor synaptotagmi…
View article: All-optical visualization of specific molecules in the ultrastructural context of brain tissue
All-optical visualization of specific molecules in the ultrastructural context of brain tissue Open
Summary Understanding the molecular anatomy and neural connectivity of the brain requires imaging technologies that can map the 3D nanoscale distribution of specific proteins in the context of brain ultrastructure. Light and electron micro…
View article: Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release
Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release Open
Significance The speed of neural information processing in the human central nervous system is ultimately determined by the speed of chemical transmission at synapses, because action potentials have relatively short distances to traverse. …
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: Synaptotagmin rings as high sensitivity regulators of synaptic vesicle docking and fusion
Synaptotagmin rings as high sensitivity regulators of synaptic vesicle docking and fusion Open
Synchronous release at neuronal synapses is accomplished by a machinery that senses calcium influx and fuses the synaptic vesicle and plasma membranes to release neurotransmitters. Previous studies suggested the calcium sensor Synaptotagmi…
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: Symmetrical arrangement of proteins under release-ready vesicles in presynaptic terminals
Symmetrical arrangement of proteins under release-ready vesicles in presynaptic terminals Open
Significance Neuronal cells maintain a small number of synaptic vesicles (SVs) that are “primed,” i.e., ready to release upon receiving the triggering signal to allow for tightly regulated and rapid release of neurotransmitters. The protei…
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…
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 membrane-bridging complexes formed by SNARE proteins - VAMP2 on the vesicle and Syntaxin-1/SNAP25 on the pre-synaptic membrane. Accumulating evidence suggest that chaperones Munc18-1 and Munc13-1 co-o…
View article: Vesicle capture by discrete self-assembled clusters of membrane-bound Munc13
Vesicle capture by discrete self-assembled clusters of membrane-bound Munc13 Open
Munc13 is a large banana-shaped soluble protein that is involved in the regulation of synaptic vesicle docking and fusion. Recent studies suggested that multiple copies of Munc13 form nanoassemblies in active zones of neurons. However, it …
View article: The golgin family exhibits a propensity to form condensates in living cells
The golgin family exhibits a propensity to form condensates in living cells Open
The Golgi is surrounded by a ribosome‐excluding matrix. Recently, we reported that the cis‐Golgi‐localized golgin GM130 can phase‐separate to form dynamic, liquid‐like condensates in vitro and in vivo . Here, we show that the overexpressio…