Journal Article

DZNE-2020-07042

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Critical role for Piccolo in synaptic vesicle retrieval.

Ackermann, F. (First author)DZNE* ; Schink, K. O. ; Bruns, C.DZNE* ; Izsvák, Z. ; Hamra, F. K. ; Rosenmund, C. ; Garner, C. C. (Last author)DZNE*

2019
eLife Sciences Publications Cambridge

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Please use a persistent id in citations: doi:10.7554/eLife.46629

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.

Keyword(s): 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)

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Contributing Institute(s):

1. Synaptopathy (AG Garner)
2. Astrocyte - Synapse Interactions (AG Ackermann)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2019

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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