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| Open AccessTau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles
Using single-molecule super-resolution microscopy, researchers revealed that Tau controls the recycling pool of synaptic vesicles in hippocampal neurons by forming nanoscale biomolecular condensates that are dynamically regulated by neuronal activity.
- Shanley F. Longfield
- , Mahdie Mollazade
- & Ramón Martínez-Mármol
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Article
| Open AccessReversal of cell, circuit and seizure phenotypes in a mouse model of DNM1 epileptic encephalopathy
One third of all epilepsies are treatment-resistant. Here, the authors show in a genetic model of epilepsy that a repurposed drug can correct cell defects, brain circuits and seizure-like events by accelerating endocytosis.
- Katherine Bonnycastle
- , Katharine L. Dobson
- & Michael A. Cousin
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| Open AccessExtracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R
Synapses are surrounded by an extracellular matrix (ECM) of extremely long-lived proteins that is thought to only be remodeled by proteolysis and de novo synthesis. Here, the authors show an alternative molecular recycling mechanism that occurs for the key ECM protein Tenascin-R.
- Tal M. Dankovich
- , Rahul Kaushik
- & Silvio O. Rizzoli
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| Open AccessVti1a/b regulate synaptic vesicle and dense core vesicle secretion via protein sorting at the Golgi
Vti1a and Vti1b are SNARE proteins implicated in regulated secretion. Here the authors show that Vti1a and Vti1b control protein sorting at the Golgi, and targeting to the axon, and thereby indirectly control regulated secretion at the synapse.
- Javier Emperador-Melero
- , Vincent Huson
- & Matthijs Verhage
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| Open AccessHeterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle docking and priming
The interaction between RIM and the C2A domain of Munc13 is known to be required for synaptic vesicle priming. Here the authors show new implications of the C2A domain of Munc13, through its dynamic interaction with RIM, in orchestrating a wide range of modulatory operations that shape vesicle docking, priming and neurotransmitter release.
- Marcial Camacho
- , Jayeeta Basu
- & Christian Rosenmund
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| Open AccessTransport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity
Transport of cargo into dendritic spines is required for synaptic plasticity. McVicker et al.describe a method of activity-dependent transport of a kinesin KIF1A and its cargo synaptotagmin-IV along microtubules that are transiently polymerized into dendritic spines.
- Derrick P. McVicker
- , Adam M. Awe
- & Erik W. Dent
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| Open AccessStructural basis of synaptic vesicle assembly promoted by α-synuclein
α-synuclein, a protein associated to Parkinson's disease, is involved in synaptic vesicle interaction and assembly. Here, the authors use NMR spectroscopy and super-resolution microscopy to unveil the nature and molecular mechanism of α-synuclein-mediated synaptic vesicle clustering.
- Giuliana Fusco
- , Tillmann Pape
- & Alfonso De Simone
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| Open AccessMechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain
Amphetamines are known to enhance extracellular dopamine levels, but the underlying mechanisms are unclear. Utilising a new pH biosensor for synaptic vesicles, the authors show that amphetamines diminish vesicle pH gradients, disrupting dopamine packaging and leading to increased neurotransmitter release.
- Zachary Freyberg
- , Mark S. Sonders
- & Jonathan A. Javitch
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| Open AccessRCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome
Down syndrome is associated with both central and peripheral nervous system dysfunction. Here, the authors report reduced sympathetic neural innervation in human Down syndrome tissues and a mouse model, and propose a role for RCAN1 trisomy in disrupted NGF receptor trafficking and neurotrophic support.
- Ami Patel
- , Naoya Yamashita
- & Rejji Kuruvilla
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Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking
Destabilizing the actin cytoskeleton induces the formation of primary cilia, but the mechanism is unknown. Here, Kim et al.show that activity of the transcriptional coactivators YAP/TAZ is regulated by actin remodelling factors, and YAP/TAZ activity correlates with ciliogenesis.
- Jongshin Kim
- , Haiin Jo
- & Joon Kim
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Small molecule-mediated stabilization of vesicle-associated helical α-synuclein inhibits pathogenic misfolding and aggregation
Small molecules that inhibit α-synuclein misfolding may have potential in the treatment of Parkinson’s disease. Fonseca-Ornelas et al.show that several of these molecules fail to block misfolding in the presence of membrane vesicles, and reveal how phtalocyanine tetrasulfonate, in contrast, overcomes this effect.
- Luis Fonseca-Ornelas
- , Sybille E. Eisbach
- & Markus Zweckstetter
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Vesicles derived via AP-3-dependent recycling contribute to asynchronous release and influence information transfer
Neurotransmitter release involves a fast synchronous component and a slower asynchronous phase, which is poorly understood. Evstratova et al.show that asynchronous release increases the precision of postsynaptic action potential firing in an activity-dependent manner, which is dependent on adaptor protein 3.
- Alesya Evstratova
- , Simon Chamberland
- & Katalin Tóth