Levels of Par-1 kinase determine the localization of Bruchpilot at the Drosophila neuromuscular junction synapses

Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh Wairkar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number16099
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Neuromuscular Junction
Synapses
Drosophila
Phosphotransferases
Synaptic Vesicles
Axons
Mitochondria
Proteins
Transport Vesicles
Axonal Transport
Nervous System Diseases
Neurodegenerative Diseases

ASJC Scopus subject areas

  • General

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Levels of Par-1 kinase determine the localization of Bruchpilot at the Drosophila neuromuscular junction synapses. / Barber, Kara R.; Hruska, Martin; Bush, Keegan M.; Martinez, Jade A.; Fei, Hong; Levitan, Irwin B.; Dalva, Matthew B.; Wairkar, Yogesh.

In: Scientific Reports, Vol. 8, No. 1, 16099, 01.12.2018.

Research output: Contribution to journalArticle

Barber, Kara R. ; Hruska, Martin ; Bush, Keegan M. ; Martinez, Jade A. ; Fei, Hong ; Levitan, Irwin B. ; Dalva, Matthew B. ; Wairkar, Yogesh. / Levels of Par-1 kinase determine the localization of Bruchpilot at the Drosophila neuromuscular junction synapses. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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