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 Mutations in Synaptojanin Disrupt Synaptic Vesicle Recycling

2000 ◽  
Vol 150 (3) ◽  
pp. 589-600 ◽  
Author(s):  
Todd W. Harris ◽  
Erika Hartwieg ◽  
H. Robert Horvitz ◽  
Erik M. Jorgensen
Keyword(s):  
Plasma Membrane ◽  
Caenorhabditis Elegans ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Vesicle Trafficking ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Synaptojanin 1

Synaptojanin is a polyphosphoinositide phosphatase that is found at synapses and binds to proteins implicated in endocytosis. For these reasons, it has been proposed that synaptojanin is involved in the recycling of synaptic vesicles. Here, we demonstrate that the unc-26 gene encodes the Caenorhabditis elegans ortholog of synaptojanin. unc-26 mutants exhibit defects in vesicle trafficking in several tissues, but most defects are found at synaptic termini. Specifically, we observed defects in the budding of synaptic vesicles from the plasma membrane, in the uncoating of vesicles after fission, in the recovery of vesicles from endosomes, and in the tethering of vesicles to the cytoskeleton. Thus, these results confirm studies of the mouse synaptojanin 1 mutants, which exhibit defects in the uncoating of synaptic vesicles (Cremona, O., G. Di Paolo, M.R. Wenk, A. Luthi, W.T. Kim, K. Takei, L. Daniell, Y. Nemoto, S.B. Shears, R.A. Flavell, D.A. McCormick, and P. De Camilli. 1999. Cell. 99:179–188), and further demonstrate that synaptojanin facilitates multiple steps of synaptic vesicle recycling.

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 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 Endophilin A and B Join Forces With Clathrin to Mediate Synaptic Vesicle Recycling in Caenorhabditis elegans

2018 ◽  
Vol 11 ◽  
Author(s):  
Szi-chieh Yu ◽  
Barbara Jánosi ◽  
Jana F. Liewald ◽  
Sebastian Wabnig ◽  
Alexander Gottschalk
Keyword(s):  
Caenorhabditis Elegans ◽  
Synaptic Vesicle ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling

scholarly journals How do you recognize and reconstitute a synaptic vesicle after fusion?

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1734 ◽  
Author(s):  
Natali L. Chanaday ◽  
Ege T. Kavalali
Keyword(s):  
Plasma Membrane ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Membrane Composition ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Molecular Identity ◽  
Daunting Task ◽  
Vesicle Biogenesis ◽  
Vesicle Cycle

Synaptic vesicle recycling is essential for sustained and reliable neurotransmission. A key component of synaptic vesicle recycling is the synaptic vesicle biogenesis process that is observed in synapses and that maintains the molecular identity of synaptic vesicles. However, the mechanisms by which synaptic vesicles are retrieved and reconstituted after fusion remain unclear. The complex molecular composition of synaptic vesicles renders their rapid biogenesis a daunting task. Therefore, in this context, kiss-and-run type transient fusion of synaptic vesicles with the plasma membrane without loss of their membrane composition and molecular identity remains a viable hypothesis that can account for the fidelity of the synaptic vesicle cycle. In this article, we discuss the biological implications of this problem as well as its possible molecular solutions.

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