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@ARTICLE{Ackermann:140720,
      author       = {Ackermann, Frauke and Schink, Kay Oliver and Bruns,
                      Christine and Izsvák, Zsuzsanna and Hamra, F Kent and
                      Rosenmund, Christian and Garner, Craig Curtis},
      title        = {{C}ritical role for {P}iccolo in synaptic vesicle
                      retrieval.},
      journal      = {eLife},
      volume       = {8},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {DZNE-2020-07042},
      pages        = {e46629},
      year         = {2019},
      abstract     = {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.},
      keywords     = {Animals / Axons: metabolism / Cytoskeletal Proteins:
                      metabolism / DNA Transposable Elements: genetics /
                      Endosomes: metabolism / GTP Phosphohydrolases: metabolism /
                      Gene Knockout Techniques / Guanosine Diphosphate: metabolism
                      / Models, Biological / Mutagenesis: genetics /
                      Neuropeptides: metabolism / Phosphatidylinositol Phosphates:
                      metabolism / Rats / Synaptic Vesicles: metabolism / Synaptic
                      Vesicles: ultrastructure / Synaptophysin: metabolism /
                      Vesicular Transport Proteins: metabolism / rab5 GTP-Binding
                      Proteins: metabolism},
      cin          = {AG Garner / AG Ackermann},
      ddc          = {600},
      cid          = {I:(DE-2719)1810001 / I:(DE-2719)1813004},
      pnm          = {341 - Molecular Signaling (POF3-341)},
      pid          = {G:(DE-HGF)POF3-341},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31074746},
      pmc          = {pmc:PMC6541439},
      doi          = {10.7554/eLife.46629},
      url          = {https://pub.dzne.de/record/140720},
}