140720 20240430120011.0 10.7554/eLife.46629 doi pmid:31074746 pmid pmc:PMC6541439 pmc altmetric:60251519 altmetric DZNE-2020-07042 English 600 Ackermann, Frauke P:(DE-2719)2810967 0 First author dzne Critical role for Piccolo in synaptic vesicle retrieval. Cambridge 2019 eLife Sciences Publications online Crossref eLife Sciences Publications, Ltd 2019-05-10 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1714464544_8220 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Loss of function of the active zone protein Piccolo has recently been linked to a disease, Pontocerebellar Hypoplasia type 3, which causes brain atrophy. Here, we address how Piccolo inactivation in rat neurons adversely affects synaptic function and thus may contribute to neuronal loss. Our analysis shows that Piccolo is critical for the recycling and maintenance of synaptic vesicles. We find that boutons lacking Piccolo have deficits in the Rab5/EEA1 dependent formation of early endosomes and thus the recycling of SVs. Mechanistically, impaired Rab5 function was caused by reduced synaptic recruitment of Pra1, known to interact selectively with the zinc finger domains of Piccolo. Importantly, over-expression of GTPase deficient Rab5 or the Znf1 domain of Piccolo restores the size and recycling of SV pools. These data provide a molecular link between the active zone and endosome sorting at synapses providing hints to how Piccolo contributes to developmental and psychiatric disorders. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 2019-05-10 Crossref http://creativecommons.org/licenses/by/4.0/ Dataset connected to CrossRef, PubMed, Animals MeSH Axons: metabolism MeSH Cytoskeletal Proteins: metabolism MeSH DNA Transposable Elements: genetics MeSH Endosomes: metabolism MeSH GTP Phosphohydrolases: metabolism MeSH Gene Knockout Techniques MeSH Guanosine Diphosphate: metabolism MeSH Models, Biological MeSH Mutagenesis: genetics MeSH Neuropeptides: metabolism MeSH Phosphatidylinositol Phosphates: metabolism MeSH Rats MeSH Synaptic Vesicles: metabolism MeSH Synaptic Vesicles: ultrastructure MeSH Synaptophysin: metabolism MeSH Vesicular Transport Proteins: metabolism MeSH rab5 GTP-Binding Proteins: metabolism MeSH Schink, Kay Oliver P:(DE-HGF)0 1 Bruns, Christine P:(DE-2719)2811027 2 dzne Izsvák, Zsuzsanna 3 Hamra, F Kent 4 Rosenmund, Christian 5 Garner, Craig Curtis P:(DE-2719)2810922 6 Last author dzne 10.7554/elife.46629 : eLife Sciences Publications, Ltd, 2019-05-10 journal-article Crossref eLife 8 2019 2050-084X 10.7554/eLife.46629 Vol. 8, p. e46629 PERI:(DE-600)2687154-3 8<e46629 e46629 eLife 8 2019 2050-084X OpenAccess http://pub.dzne.de/record/140720/files/DZNE-2020-07042.pdf OpenAccess pdfa http://pub.dzne.de/record/140720/files/DZNE-2020-07042.pdf?subformat=pdfa Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541439 oai:pub.dzne.de:140720 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2810967 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2811027 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2810922 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 0 2019 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-23 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-23 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-23 DBCoverage StatID:(DE-HGF)1040 StatID Zoological Record 2022-11-23 JCR StatID:(DE-HGF)0100 StatID ELIFE : 2021 2022-11-23 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2022-09-23T12:20:44Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2022-09-23T12:20:44Z DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-23 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-23 IF >= 5 StatID:(DE-HGF)9905 StatID ELIFE : 2021 2022-11-23 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-23 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-23 I:(DE-2719)1810001 AG Garner Synaptopathy 0 I:(DE-2719)1813004 AG Ackermann Astrocyte - Synapse Interactions 1 journal VDB UNRESTRICTED I:(DE-2719)1810001 I:(DE-2719)1813004 FullTexts -- missing cx lookup -- 10.1074/jbc.M009073200 Crossref 10.1074/jbc.M009073200 -- missing cx lookup -- 10.15252/embr.201540434 Crossref 10.15252/embr.201540434 -- missing cx lookup -- 10.1212/WNL.0000000000001523 Crossref 10.1212/WNL.0000000000001523 -- missing cx lookup -- 10.1523/JNEUROSCI.0187-13.2013 Crossref 10.1523/JNEUROSCI.0187-13.2013 -- missing cx lookup -- 10.1152/physrev.00028.2012 Crossref 10.1152/physrev.00028.2012 -- missing cx lookup -- 10.1038/336185a0 Crossref 10.1038/336185a0 -- missing cx lookup -- 10.1093/cercor/bhp170 Crossref 10.1093/cercor/bhp170 -- missing cx lookup -- 10.1371/journal.pone.0006529 Crossref 10.1371/journal.pone.0006529 1996 Crossref Cases-Langhoff 1996 -- missing cx lookup -- 10.1016/j.biopsych.2010.09.042 Crossref 10.1016/j.biopsych.2010.09.042 -- missing cx lookup -- 10.1038/17618 Crossref 10.1038/17618 -- missing cx lookup -- 10.1016/j.neuron.2014.02.012 Crossref 10.1016/j.neuron.2014.02.012 -- missing cx lookup -- 10.1016/S0896-6273(00)80883-1 Crossref 10.1016/S0896-6273(00)80883-1 -- missing cx lookup -- 10.1074/jbc.M210792200 Crossref 10.1074/jbc.M210792200 -- missing cx lookup -- 10.1016/S0736-5748(02)00046-1 Crossref 10.1016/S0736-5748(02)00046-1 -- missing cx lookup -- 10.1093/emboj/19.17.4577 Crossref 10.1093/emboj/19.17.4577 -- missing cx lookup -- 10.1016/j.neuroscience.2015.05.047 Crossref 10.1016/j.neuroscience.2015.05.047 -- missing cx lookup -- 10.1016/j.celrep.2013.10.039 Crossref 10.1016/j.celrep.2013.10.039 -- missing cx lookup -- 10.3389/fnsyn.2015.00019 Crossref 10.3389/fnsyn.2015.00019 -- missing cx lookup -- 10.1055/s-2002-20422 Crossref 10.1055/s-2002-20422 -- missing cx lookup -- 10.1083/jcb.150.3.589 Crossref 10.1083/jcb.150.3.589 -- missing cx lookup -- 10.1073/pnas.0712171105 Crossref 10.1073/pnas.0712171105 -- missing cx lookup -- 10.1083/jcb.57.2.315 Crossref 10.1083/jcb.57.2.315 -- missing cx lookup -- 10.1073/pnas.1007037107 Crossref 10.1073/pnas.1007037107 -- missing cx lookup -- 10.1016/S0092-8674(00)80380-3 Crossref 10.1016/S0092-8674(00)80380-3 -- missing cx lookup -- 10.1109/MCSE.2007.55 Crossref 10.1109/MCSE.2007.55 -- missing cx lookup -- 10.1074/jbc.M909309199 Crossref 10.1074/jbc.M909309199 -- missing cx lookup -- 10.1038/nmeth.1461 Crossref 10.1038/nmeth.1461 -- missing cx lookup -- 10.1074/jbc.M212287200 Crossref 10.1074/jbc.M212287200 -- missing cx lookup -- 10.1101/gad.13.11.1475 Crossref 10.1101/gad.13.11.1475 -- missing cx lookup -- 10.1083/jcb.200711167 Crossref 10.1083/jcb.200711167 -- missing cx lookup -- 10.1016/j.neuron.2007.10.032 Crossref 10.1016/j.neuron.2007.10.032 2010 Crossref McKinney 2010 -- missing cx lookup -- 10.1016/S0960-9822(98)70018-1 Crossref 10.1016/S0960-9822(98)70018-1 -- missing cx lookup -- 10.1016/s0091-679x(03)01007-0 Crossref 10.1016/s0091-679x(03)01007-0 -- missing cx lookup -- 10.1101/405985 Crossref 10.1101/405985 -- missing cx lookup -- 10.1016/j.neuron.2011.08.029 Crossref 10.1016/j.neuron.2011.08.029 -- missing cx lookup -- 10.1016/j.jad.2012.01.028 Crossref 10.1016/j.jad.2012.01.028 -- missing cx lookup -- 10.1371/journal.pbio.1000136 Crossref 10.1371/journal.pbio.1000136 -- missing cx lookup -- 10.1073/pnas.1000843107 Crossref 10.1073/pnas.1000843107 -- missing cx lookup -- 10.1073/pnas.1002307107 Crossref 10.1073/pnas.1002307107 -- missing cx lookup -- 10.1523/JNEUROSCI.2038-18.2019 Crossref 10.1523/JNEUROSCI.2038-18.2019 -- missing cx lookup -- 10.1038/nature19326 Crossref 10.1038/nature19326 -- missing cx lookup -- 10.1038/srep27935 Crossref 10.1038/srep27935 -- missing cx lookup -- 10.1016/j.neuron.2017.01.026 Crossref 10.1016/j.neuron.2017.01.026 -- missing cx lookup -- 10.4161/sgtp.2.2.15201 Crossref 10.4161/sgtp.2.2.15201 -- missing cx lookup -- 10.1038/nrm1500 Crossref 10.1038/nrm1500 -- missing cx lookup -- 10.3389/fncel.2014.00259 Crossref 10.3389/fncel.2014.00259 -- missing cx lookup -- 10.1523/JNEUROSCI.22-24-10680.2002 Crossref 10.1523/JNEUROSCI.22-24-10680.2002 -- missing cx lookup -- 10.1101/cshperspect.a005645 Crossref 10.1101/cshperspect.a005645 -- missing cx lookup -- 10.1038/nmeth.2019 Crossref 10.1038/nmeth.2019 -- missing cx lookup -- 10.1002/bies.201300064 Crossref 10.1002/bies.201300064 -- missing cx lookup -- 10.1146/annurev-cellbio-111315-125349 Crossref 10.1146/annurev-cellbio-111315-125349 -- missing cx lookup -- 10.1038/415321a Crossref 10.1038/415321a -- missing cx lookup -- 10.1016/S0896-6273(03)00667-6 Crossref 10.1016/S0896-6273(03)00667-6 -- missing cx lookup -- 10.1038/28879 Crossref 10.1038/28879 -- missing cx lookup -- 10.1038/380531a0 Crossref 10.1038/380531a0 -- missing cx lookup -- 10.1515/BC.2009.056 Crossref 10.1515/BC.2009.056 -- missing cx lookup -- 10.1002/j.1460-2075.1994.tb06381.x Crossref 10.1002/j.1460-2075.1994.tb06381.x -- missing cx lookup -- 10.1016/0092-8674(95)90120-5 Crossref 10.1016/0092-8674(95)90120-5 -- missing cx lookup -- 10.1038/nrm2728 Crossref 10.1038/nrm2728 -- missing cx lookup -- 10.1101/cshperspect.a005637 Crossref 10.1101/cshperspect.a005637 -- missing cx lookup -- 10.1038/mp.2008.125 Crossref 10.1038/mp.2008.125 -- missing cx lookup -- 10.1254/fpj.119.163 Crossref 10.1254/fpj.119.163 -- missing cx lookup -- 10.1371/journal.pone.0167535 Crossref 10.1371/journal.pone.0167535 -- missing cx lookup -- 10.1016/j.cell.2011.02.039 Crossref 10.1016/j.cell.2011.02.039 -- missing cx lookup -- 10.1016/S0896-6273(03)00644-5 Crossref 10.1016/S0896-6273(03)00644-5 -- missing cx lookup -- 10.1371/journal.pone.0120093 Crossref 10.1371/journal.pone.0120093 -- missing cx lookup -- 10.1523/JNEUROSCI.1835-11.2011 Crossref 10.1523/JNEUROSCI.1835-11.2011 -- missing cx lookup -- 10.1038/emboj.2013.27 Crossref 10.1038/emboj.2013.27 -- missing cx lookup -- 10.1083/jcb.147.1.151 Crossref 10.1083/jcb.147.1.151 -- missing cx lookup -- 10.1038/nature12809 Crossref 10.1038/nature12809 -- missing cx lookup -- 10.1371/journal.pone.0061494 Crossref 10.1371/journal.pone.0061494 -- missing cx lookup -- 10.1083/jcb.200211087 Crossref 10.1083/jcb.200211087 -- missing cx lookup -- 10.1038/35052055 Crossref 10.1038/35052055