scholarly journals APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development

Cell Reports ◽  
2017 ◽  
Vol 21 (12) ◽  
pp. 3596-3611 ◽  
Author(s):  
Alessandra Piccini ◽  
Enrico Castroflorio ◽  
Pierluigi Valente ◽  
Fabrizia C. Guarnieri ◽  
Davide Aprile ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Development ◽  
Vesicle Trafficking ◽  
Interacting Protein

scholarly journals Calcium-Dependent Synaptic Vesicle Trafficking Underlies Indefatigable Release at the Hair Cell Afferent Fiber Synapse

Neuron ◽  
2011 ◽  
Vol 70 (2) ◽  
pp. 326-338 ◽  
Author(s):  
Michael E. Schnee ◽  
Joseph Santos-Sacchi ◽  
Manuel Castellano-Muñoz ◽  
Jee-Hyun Kong ◽  
Anthony J. Ricci
Keyword(s):  
Hair Cell ◽  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Afferent Fiber ◽  
Calcium Dependent

scholarly journals DIP-2 suppresses ectopic neurite sprouting and axonal regeneration in mature neurons

2018 ◽  
Vol 218 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Nathaniel Noblett ◽  
Zilu Wu ◽  
Zhao Hua Ding ◽  
Seungmee Park ◽  
Tony Roenspies ◽  
...  
Keyword(s):  
Axonal Regeneration ◽  
Neuronal Development ◽  
Adult Life ◽  
Progressive Increase ◽  
Binding Domain ◽  
Neuronal Morphology ◽  
Loss Of Function ◽  
Neuron Morphology ◽  
Interacting Protein ◽  
Mature Neurons

Neuronal morphology and circuitry established during early development must often be maintained over the entirety of animal lifespans. Compared with neuronal development, the mechanisms that maintain mature neuronal structures and architecture are little understood. The conserved disco-interacting protein 2 (DIP2) consists of a DMAP1-binding domain and two adenylate-forming domains (AFDs). We show that the Caenorhabditis elegans DIP-2 maintains morphology of mature neurons. dip-2 loss-of-function mutants display a progressive increase in ectopic neurite sprouting and branching during late larval and adult life. In adults, dip-2 also inhibits initial stages of axon regeneration cell autonomously and acts in parallel to DLK-1 MAP kinase and EFA-6 pathways. The function of DIP-2 in maintenance of neuron morphology and in axon regrowth requires its AFD domains and is independent of its DMAP1-binding domain. Our findings reveal a new conserved regulator of neuronal morphology maintenance and axon regrowth after injury.

Recent Breakthroughs in Neurotransmitter Release: Paradigm for Regulated Exocytosis?

Physiology ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 42-46
Author(s):  
G Thiel
Keyword(s):  
Synaptic Vesicle ◽  
Brain Function ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Vesicle Trafficking ◽  
Regulated Exocytosis ◽  
Intracellular Vesicle ◽  
Vesicle Cycle ◽  
Synaptic Vesicle Cycle

Synaptic vesicles play a fundamental role in brain function by mediating the release of neurotransmitters. Neurons do not use an entirely unique secretion apparatus but rather a modification of the general secretion machinery. Moreover, the synaptic vesicle cycle has many similarities with intracellular vesicle trafficking pathways.

scholarly journals TBC1D24-TLDc-related epilepsy exercise-induced dystonia: rescue by antioxidants in a disease model

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2319-2335 ◽  
Author(s):  
Kevin Lüthy ◽  
Davide Mei ◽  
Baptiste Fischer ◽  
Maurizio De Fusco ◽  
Jef Swerts ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Disease Model ◽  
Stress Sensitivity ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Rolandic Epilepsy ◽  
Compound Heterozygous Mutations ◽  
Exercise Induced

AbstractGenetic mutations in TBC1D24 have been associated with multiple phenotypes, with epilepsy being the main clinical manifestation. The TBC1D24 protein consists of the unique association of a Tre2/Bub2/Cdc16 (TBC) domain and a TBC/lysin motif domain/catalytic (TLDc) domain. More than 50 missense and loss-of-function mutations have been described and are spread over the entire protein. Through whole genome/exome sequencing we identified compound heterozygous mutations, R360H and G501R, within the TLDc domain, in an index family with a Rolandic epilepsy exercise-induced dystonia phenotype (http://omim.org/entry/608105). A 20-year long clinical follow-up revealed that epilepsy was self-limited in all three affected patients, but exercise-induced dystonia persisted into adulthood in two. Furthermore, we identified three additional sporadic paediatric patients with a remarkably similar phenotype, two of whom had compound heterozygous mutations consisting of an in-frame deletion I81_K84 and an A500V mutation, and the third carried T182M and G511R missense mutations, overall revealing that all six patients harbour a missense mutation in the subdomain of TLDc between residues 500 and 511. We solved the crystal structure of the conserved Drosophila TLDc domain. This allowed us to predict destabilizing effects of the G501R and G511R mutations and, to a lesser degree, of R360H and potentially A500V. Next, we characterized the functional consequences of a strong and a weak TLDc mutation (TBC1D24G501R and TBC1D24R360H) using Drosophila, where TBC1D24/Skywalker regulates synaptic vesicle trafficking. In a Drosophila model neuronally expressing human TBC1D24, we demonstrated that the TBC1D24G501R TLDc mutation causes activity-induced locomotion and synaptic vesicle trafficking defects, while TBC1D24R360H is benign. The neuronal phenotypes of the TBC1D24G501R mutation are consistent with exacerbated oxidative stress sensitivity, which is rescued by treating TBC1D24G501R mutant animals with antioxidants N-acetylcysteine amide or α-tocopherol as indicated by restored synaptic vesicle trafficking levels and sustained behavioural activity. Our data thus show that mutations in the TLDc domain of TBC1D24 cause Rolandic-type focal motor epilepsy and exercise-induced dystonia. The humanized TBC1D24G501R fly model exhibits sustained activity and vesicle transport defects. We propose that the TBC1D24/Sky TLDc domain is a reactive oxygen species sensor mediating synaptic vesicle trafficking rates that, when dysfunctional, causes a movement disorder in patients and flies. The TLDc and TBC domain mutations’ response to antioxidant treatment we observed in the animal model suggests a potential for combining antioxidant-based therapeutic approaches to TBC1D24-associated disorders with previously described lipid-altering strategies for TBC domain mutations.

scholarly journals A New Kinetic Framework for Synaptic Vesicle Trafficking Tested in Synapsin Knock-Outs

2011 ◽  
Vol 31 (32) ◽  
pp. 11563-11577 ◽  
Author(s):  
T. Gabriel ◽  
E. Garcia-Perez ◽  
K. Mahfooz ◽  
J. Goni ◽  
R. Martinez-Turrillas ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Trafficking

Levetiracetam accelerates the onset of supply rate depression in synaptic vesicle trafficking

Epilepsia ◽  
2015 ◽  
Vol 56 (4) ◽  
pp. 535-545 ◽  
Author(s):  
Elizabeth García-Pérez ◽  
Kashif Mahfooz ◽  
João Covita ◽  
Aitor Zandueta ◽  
John F. Wesseling
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Supply Rate

scholarly journals Superfluous Role of Mammalian Septins 3 and 5 in Neuronal Development and Synaptic Transmission

2008 ◽  
Vol 28 (23) ◽  
pp. 7012-7029 ◽  
Author(s):  
Christopher W. Tsang ◽  
Michael Fedchyshyn ◽  
John Harrison ◽  
Hong Xie ◽  
Jing Xue ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Synaptic Vesicle ◽  
Hippocampal Neurons ◽  
Neuronal Development ◽  
Synapse Formation ◽  
Vesicle Traffic ◽  
Axon Development ◽  
Central Synapses ◽  
Synaptic Vesicle Fusion

ABSTRACT The septin family of GTPases, first identified for their roles in cell division, are also expressed in postmitotic tissues. SEPT3 (G-septin) and SEPT5 (CDCrel-1) are highly expressed in neurons, enriched in presynaptic terminals, and associated with synaptic vesicles. These characteristics suggest that SEPT3 or SEPT5 might be important for synapse formation, maturation, or synaptic vesicle traffic. Since Sept5 −/− mice do not show any overt neurological phenotypes, we generated Sept3 −/− and Sept3 −/− Sept5 −/− mice and found that SEPT3 and SEPT5 are not essential for development, fertility, or viability. Changes in the expression of septins were noted in the absence of SEPT3, SEPT5, and both septins. SEPT5 association with other septins in brain tissue was unaffected by the removal of SEPT3. No abnormalities were observed in the gross morphology and synapses of the hippocampus. Similarly, axon development and synapse formation were unaffected in vitro. In cultured hippocampal neurons, the size of the recycling synaptic vesicle pool was unaltered in the absence of SEPT3. Furthermore, synaptic transmission at two different central synapses was not significantly affected in Sept3 −/− Sept5 −/− mice. These results indicate that SEPT3 and SEPT5 are dispensable for neuronal development as well as for synaptic vesicle fusion and recycling.

scholarly journals Functional Role of ATP Binding to Synapsin I In Synaptic Vesicle Trafficking and Release Dynamics

2014 ◽  
Vol 34 (44) ◽  
pp. 14752-14768 ◽  
Author(s):  
M. Orlando ◽  
G. Lignani ◽  
L. Maragliano ◽  
A. Fassio ◽  
F. Onofri ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Functional Role ◽  
Vesicle Trafficking ◽  
Synapsin I ◽  
Atp Binding
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