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Critical role for Piccolo in synaptic vesicle retrieval

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Item Type:Preprint
Title:Critical role for Piccolo in synaptic vesicle retrieval
Creators Name:Ackermann, F. and Schink, K.O. and Bruns, C. and Izsvak, Z. and Hamra, K. and Rosenmund, C. and Garner, C.C.
Abstract:Loss of function of the presynaptic active zone protein Piccolo has recently been linked to a devastating disease causing brain atrophy. Here, we address how Piccolo inactivation adversely affects synaptic function and thus may contributes to neuronal loss. Our analysis shows that Piccolo is critical for the activity dependent recycling and maintenance of synaptic vesicles (SVs). Specifically, 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 the reduced synaptic recruitment of Pra1, known to interact selectively with the zinc fingers 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 both developmental and psychiatric disorders.
Keywords:Piccolo, Pra1, Rab5, EEA1, Synaptic Vesicles, Endosomes
Publisher:Cold Spring Harbor Laboratory Press
Article Number:330050
Date:24 May 2018
Official Publication:https://doi.org/10.1101/330050
Related to:
https://edoc.mdc-berlin.de/18227/Final version

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