Critical role for Piccolo in synaptic vesicle retrieval

Frauke Ackermann, Kay Oliver Schink, Christine Bruns, Zsuzsanna Izsvák, F. Kent Hamra, Christian Rosenmund, Craig Curtis Garner

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - May 10 2019
Externally publishedYes

Fingerprint

Synaptic Vesicles
Recycling
Endosomes
GTP Phosphohydrolases
Zinc Fingers
Sorting
Synapses
Neurons
Atrophy
Psychiatry
Zinc
Rats
Brain
Maintenance
Proteins

Keywords

  • early endosomes
  • neuroscience
  • Piccolo
  • Rab5
  • rat
  • recycling
  • synaptic vesicles

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Ackermann, F., Schink, K. O., Bruns, C., Izsvák, Z., Hamra, F. K., Rosenmund, C., & Garner, C. C. (2019). Critical role for Piccolo in synaptic vesicle retrieval. eLife, 8. https://doi.org/10.7554/eLife.46629

Critical role for Piccolo in synaptic vesicle retrieval. / Ackermann, Frauke; Schink, Kay Oliver; Bruns, Christine; Izsvák, Zsuzsanna; Hamra, F. Kent; Rosenmund, Christian; Garner, Craig Curtis.

In: eLife, Vol. 8, 10.05.2019.

Research output: Contribution to journalArticle

Ackermann, F, Schink, KO, Bruns, C, Izsvák, Z, Hamra, FK, Rosenmund, C & Garner, CC 2019, 'Critical role for Piccolo in synaptic vesicle retrieval', eLife, vol. 8. https://doi.org/10.7554/eLife.46629
Ackermann F, Schink KO, Bruns C, Izsvák Z, Hamra FK, Rosenmund C et al. Critical role for Piccolo in synaptic vesicle retrieval. eLife. 2019 May 10;8. https://doi.org/10.7554/eLife.46629
Ackermann, Frauke ; Schink, Kay Oliver ; Bruns, Christine ; Izsvák, Zsuzsanna ; Hamra, F. Kent ; Rosenmund, Christian ; Garner, Craig Curtis. / Critical role for Piccolo in synaptic vesicle retrieval. In: eLife. 2019 ; Vol. 8.
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