title: Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase.
abstract: 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.
authors.affiliation: George and Cynthia Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.|Neuroscience Graduate Program, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Kara R
authors.initials: KR
authors.lastname: Barber
authors.affiliation: Summer Undergraduate Research Program, UTMB, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Julia
authors.identifier: 0000-0003-4148-7364
authors.initials: J
authors.lastname: Tanquary
authors.affiliation: George and Cynthia Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.|Neuroscience Graduate Program, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Keegan
authors.identifier: 0000-0003-3237-9134
authors.initials: K
authors.lastname: Bush
authors.affiliation: George and Cynthia Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.|Neuroscience Graduate Program, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Shaw
authors.affiliation: Sealy Center for Structural Biology, UTMB, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Michael
authors.identifier: 0000-0002-8612-4527
authors.initials: M
authors.lastname: Woodson
authors.affiliation: Sealy Center for Structural Biology, UTMB, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Sherman
authors.affiliation: George and Cynthia Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.|Neuroscience Graduate Program, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Yogesh P
authors.identifier: 0000-0002-8960-9781
authors.initials: YP
authors.lastname: Wairkar
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000473:pathology; D001369:Axons / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009469:Neuromuscular Junction / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000473:pathology; D009435:Synaptic Transmission / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
chemical_list: C510146:BRP protein, Drosophila; D029721:Drosophila Proteins; D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3; C472496:Par-1 protein, Drosophila