RGD Reference Report - Critical role for Piccolo in synaptic vesicle retrieval. - Rat Genome Database

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Critical role for Piccolo in synaptic vesicle retrieval.

Authors: Ackermann, Frauke  Schink, Kay Oliver  Bruns, Christine  Izsvák, Zsuzsanna  Hamra, F Kent  Rosenmund, Christian  Garner, Craig Curtis 
Citation: Ackermann F, etal., Elife. 2019 May 10;8. pii: 46629. doi: 10.7554/eLife.46629.
RGD ID: 41408338
Pubmed: PMID:31074746   (View Abstract at PubMed)
PMCID: PMC6541439   (View Article at PubMed Central)
DOI: DOI:10.7554/eLife.46629   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PcloRatmodulation of excitatory postsynaptic potential  IMP  RGD 
PcloRatpositive regulation of synaptic vesicle recycling  IMP  RGD 
PcloRatregulation of endosome size  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rabac1Ratglutamatergic synapse is_active_inIDA PMID:31074746SynGO 
Rabac1Ratpresynapse is_active_inIDA PMID:31074746SynGO 
Eea1Ratpresynaptic endosome is_active_inIDA PMID:31074746SynGO 
Eea1Ratpresynaptic endosome is_active_inIMP PMID:31074746SynGO 
Rab5aRatpresynaptic endosome is_active_inIDA PMID:31074746SynGO 
Rab5aRatpresynaptic endosome is_active_inIMP PMID:31074746SynGO 
Rab5al1Ratpresynaptic endosome is_active_inIDA PMID:31074746SynGO 
Rab5al1Ratpresynaptic endosome is_active_inIMP PMID:31074746SynGO 
Rab7aRatpresynaptic endosome is_active_inIDA PMID:31074746SynGO 
Rab7aRatpresynaptic endosome is_active_inIMP PMID:31074746SynGO 
Rab7aRatpresynaptic endosome is_active_inNAS PMID:31074746SynGO 
Rabgef1Ratpresynaptic endosome is_active_inIDA PMID:31074746SynGO 
Rabgef1Ratpresynaptic endosome is_active_inIMP PMID:31074746SynGO 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PcloRatabnormal cerebellar glomerulus morphology  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatabnormal cerebellar glomerulus morphology  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatabnormal cerebellar glomerulus morphology  IMP compared to wild-type ratRGD 
PcloRatabnormal synaptic vesicle number  IMP  RGD 
PcloTn(sb-B-Geo)FkhRatabnormal synaptic vesicle number  IMP  RGD 
PcloRatabnormal synaptic vesicle recycling  IMP  RGD 
PcloTn(sb-B-Geo)FkhRatabnormal synaptic vesicle recycling  IMP  RGD 
PcloRatdecreased body length  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatdecreased body length  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatdecreased body length  IMP compared to wild-type ratRGD 
PcloRatdecreased body weight  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatdecreased body weight  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatdecreased body weight  IMP compared to wild-type ratRGD 
PcloRatdecreased brain weight  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatdecreased brain weight  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatdecreased brain weight  IMP compared to wild-type ratRGD 
PcloRatdecreased pons size  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatdecreased pons size  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatdecreased pons size  IMP compared to wild-type ratRGD 
PcloRatincreased excitatory postsynaptic current amplitude  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatincreased excitatory postsynaptic current amplitude  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatincreased excitatory postsynaptic current amplitude  IMP compared to wild-type ratRGD 
PcloRatsmall cerebellum  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatsmall cerebellum  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatsmall cerebellum  IMP compared to wild-type ratRGD 
PcloRatthin cerebellar granule layer  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatthin cerebellar granule layer  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatthin cerebellar granule layer  IMP compared to wild-type ratRGD 
PcloRatthin cerebellar molecular layer  IMP compared to wild-type ratRGD 
PcloTn(sb-B-Geo)FkhRatthin cerebellar molecular layer  IMP compared to wild-type ratRGD 
WI.SD-PcloTn(sb-B-Geo)FkhRatthin cerebellar molecular layer  IMP compared to wild-type ratRGD 
Objects Annotated

Genes (Rattus norvegicus)
Eea1  (early endosome antigen 1)
Pclo  (piccolo (presynaptic cytomatrix protein))
PcloTn(sb-B-Geo)Fkh  (presynaptic cytomatrix protein; sleeping beauty transposon induced mutant, Fkh)
Rab5a  (RAB5A, member RAS oncogene family)
Rab5al1  (Rab5a, member RAS oncogene family-like 1)
Rab7a  (RAB7A, member RAS oncogene family)
Rabac1  (Rab acceptor 1)
Rabgef1  (RAB guanine nucleotide exchange factor 1)


Additional Information