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Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase

Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is rel...

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Autores principales: Barber, Kara R., Tanquary, Julia, Bush, Keegan, Shaw, Amanda, Woodson, Michael, Sherman, Michael, Wairkar, Yogesh P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340405/
https://www.ncbi.nlm.nih.gov/pubmed/28222093
http://dx.doi.org/10.1371/journal.pgen.1006621
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author Barber, Kara R.
Tanquary, Julia
Bush, Keegan
Shaw, Amanda
Woodson, Michael
Sherman, Michael
Wairkar, Yogesh P.
author_facet Barber, Kara R.
Tanquary, Julia
Bush, Keegan
Shaw, Amanda
Woodson, Michael
Sherman, Michael
Wairkar, Yogesh P.
author_sort Barber, Kara R.
collection PubMed
description Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated.
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spelling pubmed-53404052017-03-27 Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase Barber, Kara R. Tanquary, Julia Bush, Keegan Shaw, Amanda Woodson, Michael Sherman, Michael Wairkar, Yogesh P. PLoS Genet Research Article Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated. Public Library of Science 2017-02-21 /pmc/articles/PMC5340405/ /pubmed/28222093 http://dx.doi.org/10.1371/journal.pgen.1006621 Text en © 2017 Barber et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Barber, Kara R.
Tanquary, Julia
Bush, Keegan
Shaw, Amanda
Woodson, Michael
Sherman, Michael
Wairkar, Yogesh P.
Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase
title Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase
title_full Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase
title_fullStr Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase
title_full_unstemmed Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase
title_short Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase
title_sort active zone proteins are transported via distinct mechanisms regulated by par-1 kinase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340405/
https://www.ncbi.nlm.nih.gov/pubmed/28222093
http://dx.doi.org/10.1371/journal.pgen.1006621
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