[{"status":"public","abstract":[{"text":"Activity-dependent bulk endocytosis generates synaptic vesicles (SVs) during intense neuronal activity via a two-step process. First, bulk endosomes are formed direct from the plasma membrane from which SVs are then generated. SV generation from bulk endosomes requires the efflux of previously accumulated calcium and activation of the protein phosphatase calcineurin. However, it is still unknown how calcineurin mediates SV generation. We addressed this question using a series of acute interventions that decoupled the generation of SVs from bulk endosomes in rat primary neuronal culture. This was achieved by either disruption of protein–protein interactions via delivery of competitive peptides, or inhibition of enzyme activity by known inhibitors. SV generation was monitored using either a morphological horseradish peroxidase assay or an optical assay that monitors the replenishment of the reserve SV pool. We found that SV generation was inhibited by, (i) peptides that disrupt calcineurin interactions, (ii) an inhibitor of dynamin I GTPase activity and (iii) peptides that disrupt the phosphorylation-dependent dynamin I–syndapin I interaction. Peptides that disrupted syndapin I interactions with eps15 homology domain-containing proteins had no effect. This revealed that (i) calcineurin must be localized at bulk endosomes to mediate its effect, (ii) dynamin I GTPase activity is essential for SV fission and (iii) the calcineurin-dependent interaction between dynamin I and syndapin I is essential for SV generation. We therefore propose that a calcineurin-dependent dephosphorylation cascade that requires both dynamin I GTPase and syndapin I lipid-deforming activity is essential for SV generation from bulk endosomes.","lang":"eng"}],"day":"01","isi":1,"doi":"10.1111/jnc.14862","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"SiHi"}],"has_accepted_license":"1","file":[{"file_size":4334962,"file_id":"7452","access_level":"open_access","creator":"dernst","relation":"main_file","checksum":"ec1fb2aebb874009bc309adaada6e1d7","file_name":"2019_JournNeurochemistry_Cheung.pdf","date_updated":"2020-07-14T12:47:47Z","content_type":"application/pdf","date_created":"2020-02-05T10:30:02Z"}],"article_type":"original","type":"journal_article","issue":"5","publisher":"Wiley","date_created":"2019-11-12T14:37:08Z","scopus_import":"1","date_published":"2019-12-01T00:00:00Z","quality_controlled":"1","oa_version":"Published Version","page":"570-583","year":"2019","article_processing_charge":"No","publication":"Journal of Neurochemistry","publication_status":"published","citation":{"short":"G.T. Cheung, M.A. Cousin, Journal of Neurochemistry 151 (2019) 570–583.","ieee":"G. T. Cheung and M. A. Cousin, “Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction,” <i>Journal of Neurochemistry</i>, vol. 151, no. 5. Wiley, pp. 570–583, 2019.","apa":"Cheung, G. T., &#38; Cousin, M. A. (2019). Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction. <i>Journal of Neurochemistry</i>. Wiley. <a href=\"https://doi.org/10.1111/jnc.14862\">https://doi.org/10.1111/jnc.14862</a>","ista":"Cheung GT, Cousin MA. 2019. Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction. Journal of Neurochemistry. 151(5), 570–583.","chicago":"Cheung, Giselle T, and Michael A. Cousin. “Synaptic Vesicle Generation from Activity‐dependent Bulk Endosomes Requires a Dephosphorylation‐dependent Dynamin–Syndapin Interaction.” <i>Journal of Neurochemistry</i>. Wiley, 2019. <a href=\"https://doi.org/10.1111/jnc.14862\">https://doi.org/10.1111/jnc.14862</a>.","ama":"Cheung GT, Cousin MA. Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction. <i>Journal of Neurochemistry</i>. 2019;151(5):570-583. doi:<a href=\"https://doi.org/10.1111/jnc.14862\">10.1111/jnc.14862</a>","mla":"Cheung, Giselle T., and Michael A. Cousin. “Synaptic Vesicle Generation from Activity‐dependent Bulk Endosomes Requires a Dephosphorylation‐dependent Dynamin–Syndapin Interaction.” <i>Journal of Neurochemistry</i>, vol. 151, no. 5, Wiley, 2019, pp. 570–83, doi:<a href=\"https://doi.org/10.1111/jnc.14862\">10.1111/jnc.14862</a>."},"file_date_updated":"2020-07-14T12:47:47Z","author":[{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","orcid":"0000-0001-8457-2572","last_name":"Cheung","full_name":"Cheung, Giselle T"},{"last_name":"Cousin","full_name":"Cousin, Michael A.","first_name":"Michael A."}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0022-3042"],"eissn":["1471-4159"]},"oa":1,"volume":151,"month":"12","external_id":{"pmid":["31479508"],"isi":["000490703100001"]},"title":"Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction","intvolume":"       151","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_updated":"2023-08-30T07:21:50Z","_id":"7005","pmid":1},{"scopus_import":"1","publisher":"Wiley-Blackwell","date_created":"2018-12-11T11:58:46Z","date_published":"2003-06-01T00:00:00Z","quality_controlled":"1","issue":"5","type":"journal_article","extern":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","doi":"10.1046/j.1471-4159.2003.01751.x","publist_id":"4268","article_type":"original","day":"01","status":"public","abstract":[{"text":"Cyclic ADP-ribose (cADP-ribose) is a putative second messenger or modulator. However, the role of cADP-ribose in the downstream signals of the metabotropic glutamate receptors (mGluRs) is unclear. Here, we show that glutamate stimulates ADP-ribosyl cyclase activity in rat or mouse crude membranes of retina via group III mGluRs or in superior cervical ganglion via group I mGluRs. The retina of mGluR6-deficient mice showed no increase in the ADP-ribosyl cyclase level in response to glutamate. GTP enhanced the initial rate of basal and glutamate-stimulated cyclase activity. GTP-γ-S also stimulated basal activity. To determine whether the coupling mode of mGluRs to ADP-ribosyl cyclase is a feature common to individual cloned mGluRs, we expressed each mGluR subtype in NG108-15 neuroblastoma x glioma hybrid cells. The glutamate-induced stimulation of the cyclase occurs preferentially in NG108-15 cells over-expressing mGluRs1, 3, 5, and 6. Cells expressing mGluR2 or mGluRs4 and 7 exhibit inhibition or no coupling, respectively. Glutamate-induced activation or inhibition of the cyclase activity was eliminated after pre-treatment with cholera or pertussis toxin, respectively. Thus, the subtype-specific coupling of mGluRs to ADP-ribosyl cyclase via G proteins suggests that some glutamate-evoked neuronal functions are mediated by cADP-ribose.","lang":"eng"}],"pmid":1,"OA_type":"closed access","date_updated":"2026-05-22T11:05:45Z","_id":"2631","intvolume":"        85","title":"Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells","volume":85,"month":"06","external_id":{"pmid":["12753074"]},"author":[{"last_name":"Higashida","full_name":"Higashida, Haruhiro","first_name":"Haruhiro"},{"full_name":"Zhang, Jia","last_name":"Zhang","first_name":"Jia"},{"last_name":"Mochida","full_name":"Mochida, Sumiko","first_name":"Sumiko"},{"full_name":"Chen, Xiao","last_name":"Chen","first_name":"Xiao"},{"last_name":"Shin","full_name":"Shin, Yeonsook","first_name":"Yeonsook"},{"last_name":"Noda","full_name":"Noda, Mami","first_name":"Mami"},{"first_name":"Kazi","last_name":"Hossain","full_name":"Hossain, Kazi"},{"last_name":"Hoshi","full_name":"Hoshi, Naoto","first_name":"Naoto"},{"first_name":"Minako","last_name":"Hashii","full_name":"Hashii, Minako"},{"first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto"},{"last_name":"Nakanishi","full_name":"Nakanishi, Shigetada","first_name":"Shigetada"},{"first_name":"Yutaka","full_name":"Fukuda, Yutaka","last_name":"Fukuda"},{"first_name":"Shigeru","full_name":"Yokoyama, Shigeru","last_name":"Yokoyama"}],"publication_identifier":{"eissn":["1471-4159"],"issn":["0022-3042"]},"language":[{"iso":"eng"}],"publication":"Journal of Neurochemistry","citation":{"apa":"Higashida, H., Zhang, J., Mochida, S., Chen, X., Shin, Y., Noda, M., … Yokoyama, S. (2003). Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells. <i>Journal of Neurochemistry</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1046/j.1471-4159.2003.01751.x\">https://doi.org/10.1046/j.1471-4159.2003.01751.x</a>","ista":"Higashida H, Zhang J, Mochida S, Chen X, Shin Y, Noda M, Hossain K, Hoshi N, Hashii M, Shigemoto R, Nakanishi S, Fukuda Y, Yokoyama S. 2003. Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells. Journal of Neurochemistry. 85(5), 1148–1158.","ieee":"H. Higashida <i>et al.</i>, “Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells,” <i>Journal of Neurochemistry</i>, vol. 85, no. 5. Wiley-Blackwell, pp. 1148–1158, 2003.","short":"H. Higashida, J. Zhang, S. Mochida, X. Chen, Y. Shin, M. Noda, K. Hossain, N. Hoshi, M. Hashii, R. Shigemoto, S. Nakanishi, Y. Fukuda, S. Yokoyama, Journal of Neurochemistry 85 (2003) 1148–1158.","mla":"Higashida, Haruhiro, et al. “Subtype-Specific Coupling with ADP-Ribosyl Cyclase of Metabotropic Glutamate Receptors in Retina, Cervical Superior Ganglion and NG108-15 Cells.” <i>Journal of Neurochemistry</i>, vol. 85, no. 5, Wiley-Blackwell, 2003, pp. 1148–58, doi:<a href=\"https://doi.org/10.1046/j.1471-4159.2003.01751.x\">10.1046/j.1471-4159.2003.01751.x</a>.","ama":"Higashida H, Zhang J, Mochida S, et al. Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells. <i>Journal of Neurochemistry</i>. 2003;85(5):1148-1158. doi:<a href=\"https://doi.org/10.1046/j.1471-4159.2003.01751.x\">10.1046/j.1471-4159.2003.01751.x</a>","chicago":"Higashida, Haruhiro, Jia Zhang, Sumiko Mochida, Xiao Chen, Yeonsook Shin, Mami Noda, Kazi Hossain, et al. “Subtype-Specific Coupling with ADP-Ribosyl Cyclase of Metabotropic Glutamate Receptors in Retina, Cervical Superior Ganglion and NG108-15 Cells.” <i>Journal of Neurochemistry</i>. Wiley-Blackwell, 2003. <a href=\"https://doi.org/10.1046/j.1471-4159.2003.01751.x\">https://doi.org/10.1046/j.1471-4159.2003.01751.x</a>."},"publication_status":"published","year":"2003","article_processing_charge":"No","oa_version":"None","page":"1148 - 1158"}]