Document Type

Article

Publication Date

12-1-2018

Comments

This article has been peer reviewed. It is the author’s final published version in Scientific Reports, Volume 5, Issue 3, December 2018, Article number 16099.

The published version is available at https://doi.org/10.1038/s41598-018-34250-9. Copyright © Barber et al.

Abstract

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of BRP in axons at the expense of BRP at active zones. Temporal analyses demonstrate that accumulation of BRP within axons precedes the loss of synaptic function and its depletion from the active zones. Mechanistically, we find that Par-1 co-localizes with BRP and is present in the same molecular complex, raising the possibility of a novel mechanism for selective localization of BRP-like active zone scaffolding proteins. Taken together, these data suggest an intriguing possibility that mislocalization of active zone proteins like BRP might be one of the earliest signs of synapse perturbation and perhaps, synaptic networks that precede many neurological disorders.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

30382129

Language

English

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