scholarly journals Colocalization of synapsin and actin during synaptic vesicle recycling

2003 ◽  
Vol 161 (4) ◽  
pp. 737-747 ◽  
Author(s):  
Ona Bloom ◽  
Emma Evergren ◽  
Nikolay Tomilin ◽  
Ole Kjaerulff ◽  
Peter Löw ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Synaptic Activity ◽  
Immunogold Electron Microscopy ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Reserve Pool ◽  
Giant Synapse

It has been hypothesized that in the mature nerve terminal, interactions between synapsin and actin regulate the clustering of synaptic vesicles and the availability of vesicles for release during synaptic activity. Here, we have used immunogold electron microscopy to examine the subcellular localization of actin and synapsin in the giant synapse in lamprey at different states of synaptic activity. In agreement with earlier observations, in synapses at rest, synapsin immunoreactivity was preferentially localized to a portion of the vesicle cluster distal to the active zone. During synaptic activity, however, synapsin was detected in the pool of vesicles proximal to the active zone. In addition, actin and synapsin were found colocalized in a dynamic filamentous cytomatrix at the sites of synaptic vesicle recycling, endocytic zones. Synapsin immunolabeling was not associated with clathrin-coated intermediates but was found on vesicles that appeared to be recycling back to the cluster. Disruption of synapsin function by microinjection of antisynapsin antibodies resulted in a prominent reduction of the cytomatrix at endocytic zones of active synapses. Our data suggest that in addition to its known function in clustering of vesicles in the reserve pool, synapsin migrates from the synaptic vesicle cluster and participates in the organization of the actin-rich cytomatrix in the endocytic zone during synaptic activity.

scholarly journals A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Yumei Wu ◽  
Eileen T O'Toole ◽  
Martine Girard ◽  
Brigitte Ritter ◽  
Mirko Messa ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Synaptic Activity ◽  
Synaptic Vesicle Recycling ◽  
Knock Out ◽  
Knock Down ◽  
Vesicle Recycling ◽  
Subsequent Conversion ◽  
Insight Into

The exocytosis of synaptic vesicles (SVs) elicited by potent stimulation is rapidly compensated by bulk endocytosis of SV membranes leading to large endocytic vacuoles (‘bulk’ endosomes). Subsequently, these vacuoles disappear in parallel with the reappearance of new SVs. We have used synapses of dynamin 1 and 3 double knock-out neurons, where clathrin-mediated endocytosis (CME) is dramatically impaired, to gain insight into the poorly understood mechanisms underlying this process. Massive formation of bulk endosomes was not defective, but rather enhanced, in the absence of dynamin 1 and 3. The subsequent conversion of bulk endosomes into SVs was not accompanied by the accumulation of clathrin coated buds on their surface and this process proceeded even after further clathrin knock-down, suggesting its independence of clathrin. These findings support the existence of a pathway for SV reformation that bypasses the requirement for clathrin and dynamin 1/3 and that operates during intense synaptic activity.

scholarly journals Polyunsaturated Fatty Acids Influence Synaptojanin Localization to Regulate Synaptic Vesicle Recycling

2008 ◽  
Vol 19 (3) ◽  
pp. 833-842 ◽  
Author(s):  
Esther Marza ◽  
Toni Long ◽  
Adolfo Saiardi ◽  
Marija Sumakovic ◽  
Stefan Eimer ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Endocytic Pathway ◽  
Synaptic Membranes ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Phosphoinositide Phosphatase ◽  
Low Levels

The lipid polyunsaturated fatty acids are highly enriched in synaptic membranes, including synaptic vesicles, but their precise function there is unknown. Caenorhabditis elegans fat-3 mutants lack long-chain polyunsaturated fatty acids (LC-PUFAs); they release abnormally low levels of serotonin and acetylcholine and are depleted of synaptic vesicles, but the mechanistic basis of these defects is unclear. Here we demonstrate that synaptic vesicle endocytosis is impaired in the mutants: the synaptic vesicle protein synaptobrevin is not efficiently retrieved after synaptic vesicles fuse with the presynaptic membrane, and the presynaptic terminals contain abnormally large endosomal-like compartments and synaptic vesicles. Moreover, the mutants have abnormally low levels of the phosphoinositide phosphatase synaptojanin at release sites and accumulate the main synaptojanin substrate phosphatidylinositol 4,5-bisphosphate at these sites. Both synaptobrevin and synaptojanin mislocalization can be rescued by providing exogenous arachidonic acid, an LC-PUFA, suggesting that the endocytosis defect is caused by LC-PUFA depletion. By showing that the genes fat-3 and synaptojanin act in the same endocytic pathway at synapses, our findings suggest that LC-PUFAs are required for efficient synaptic vesicle recycling, probably by modulating synaptojanin localization at synapses.

scholarly journals μ2 adaptin facilitates but is not essential for synaptic vesicle recycling in Caenorhabditis elegans

2008 ◽  
Vol 183 (5) ◽  
pp. 881-892 ◽  
Author(s):  
Mingyu Gu ◽  
Kim Schuske ◽  
Shigeki Watanabe ◽  
Qiang Liu ◽  
Paul Baum ◽  
...  
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Evoked Responses ◽  
Nematode Caenorhabditis Elegans ◽  
Synaptic Vesicle Recycling ◽  
Specific Loss ◽  
Vesicle Recycling ◽  
Cargo Proteins

Synaptic vesicles must be recycled to sustain neurotransmission, in large part via clathrin-mediated endocytosis. Clathrin is recruited to endocytic sites on the plasma membrane by the AP2 adaptor complex. The medium subunit (μ2) of AP2 binds to cargo proteins and phosphatidylinositol-4,5-bisphosphate on the cell surface. Here, we characterize the apm-2 gene (also called dpy-23), which encodes the only μ2 subunit in the nematode Caenorhabditis elegans. APM-2 is highly expressed in the nervous system and is localized to synapses; yet specific loss of APM-2 in neurons does not affect locomotion. In apm-2 mutants, clathrin is mislocalized at synapses, and synaptic vesicle numbers and evoked responses are reduced to 60 and 65%, respectively. Collectively, these data suggest AP2 μ2 facilitates but is not essential for synaptic vesicle recycling.

scholarly journals Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse

2021 ◽  
Vol 9 ◽  
Author(s):  
Kaitlyn E. Fouke ◽  
M. Elizabeth Wegman ◽  
Sarah A. Weber ◽  
Emily B. Brady ◽  
Cristina Román-Vendrell ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Significant Loss ◽  
Binding Partner ◽  
Reserve Pool ◽  
Associated Proteins ◽  
Dose Dependent ◽  
Total Membrane ◽  
Synapsin 1

Neurotransmission relies critically on the exocytotic release of neurotransmitters from small synaptic vesicles (SVs) at the active zone. Therefore, it is essential for neurons to maintain an adequate pool of SVs clustered at synapses in order to sustain efficient neurotransmission. It is well established that the phosphoprotein synapsin 1 regulates SV clustering at synapses. Here, we demonstrate that synuclein, another SV-associated protein and synapsin binding partner, also modulates SV clustering at a vertebrate synapse. When acutely introduced to unstimulated lamprey reticulospinal synapses, a pan-synuclein antibody raised against the N-terminal domain of α-synuclein induced a significant loss of SVs at the synapse. Both docked SVs and the distal reserve pool of SVs were depleted, resulting in a loss of total membrane at synapses. In contrast, antibodies against two other abundant SV-associated proteins, synaptic vesicle glycoprotein 2 (SV2) and vesicle-associated membrane protein (VAMP/synaptobrevin), had no effect on the size or distribution of SV clusters. Synuclein perturbation caused a dose-dependent reduction in the number of SVs at synapses. Interestingly, the large SV clusters appeared to disperse into smaller SV clusters, as well as individual SVs. Thus, synuclein regulates clustering of SVs at resting synapses, as well as docking of SVs at the active zone. These findings reveal new roles for synuclein at the synapse and provide critical insights into diseases associated with α-synuclein dysfunction, such as Parkinson’s disease.

scholarly journals Neuroligin-1 mediates presynaptic maturation through brain-derived neurotrophic factor signaling

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Andonia Petkova-Tuffy ◽  
Nina Gödecke ◽  
Julio Viotti ◽  
Martin Korte ◽  
Thomas Dresbach
Keyword(s):  
Cell Adhesion ◽  
Synaptic Vesicle ◽  
Neurotrophic Factor ◽  
Neurodevelopmental Disorders ◽  
Active Zone ◽  
Brain Derived Neurotrophic Factor ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Synapse Maturation ◽  
Synaptic Maturation

Abstract Background Maturation is a process that allows synapses to acquire full functionality, optimizing their activity to diverse neural circuits, and defects in synaptic maturation may contribute to neurodevelopmental disorders. Neuroligin-1 (NL1) is a postsynaptic cell adhesion molecule essential for synapse maturation, a role typically attributed to binding to pre-synaptic ligands, the neurexins. However, the pathways underlying the action of NL1 in synaptic maturation are incompletely understood, and some of its previously observed effects seem reminiscent of those described for the neurotrophin brain-derived neurotrophic factor (BDNF). Here, we show that maturational increases in active zone stability and synaptic vesicle recycling rely on the joint action of NL1 and brain-derived neurotrophic factor (BDNF). Results Applying BDNF to hippocampal neurons in primary cultures or organotypical slice cultures mimicked the effects of overexpressing NL1 on both structural and functional maturation. Overexpressing a NL1 mutant deficient in neurexin binding still induced presynaptic maturation. Like NL1, BDNF increased synaptic vesicle recycling and the augmentation of transmitter release by phorbol esters, both hallmarks of presynaptic maturation. Mimicking the effects of NL1, BDNF also increased the half-life of the active zone marker bassoon at synapses, reflecting increased active zone stability. Overexpressing NL1 increased the expression and synaptic accumulation of BDNF. Inhibiting BDNF signaling pharmacologically or genetically prevented the effects of NL1 on presynaptic maturation. Applying BDNF to NL1-knockout mouse cultures rescued defective presynaptic maturation, indicating that BDNF acts downstream of NL1 and can restore presynaptic maturation at late stages of network development. Conclusions Our data introduce BDNF as a novel and essential component in a transsynaptic pathway linking NL1-mediated cell adhesion, neurotrophin action, and presynaptic maturation. Our findings connect synaptic cell adhesion and neurotrophin signaling and may provide a therapeutic approach to neurodevelopmental disorders by targeting synapse maturation.

scholarly journals The tortoise and the hare revisited

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Natalia L Kononenko ◽  
Arndt Pechstein ◽  
Volker Haucke
Keyword(s):  
Electron Microscopy ◽  
Synaptic Vesicle ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling

Optogenetics and electron microscopy reveal an ultrafast mode of synaptic vesicle recycling, adding a new twist to a 40-year-old controversy.

The active zone protein CAST regulates synaptic vesicle recycling and quantal size in the mouse hippocampus

2016 ◽  
Vol 44 (5) ◽  
pp. 2272-2284 ◽  
Author(s):  
Shizuka Kobayashi ◽  
Yamato Hida ◽  
Hiroyoshi Ishizaki ◽  
Eiji Inoue ◽  
Miki Tanaka-Okamoto ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Quantal Size ◽  
Mouse Hippocampus
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