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Open AccessArticle

Serine–Arginine Protein Kinase SRPK2 Modulates the Assembly of the Active Zone Scaffolding Protein CAST1/ERC2

1
Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, 1240000 Antofagasta, Chile
2
Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile
3
Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany
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German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany
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Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, 6210427 Punta Arenas, Chile
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Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia
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Center for Behavioral Brain Sciences and Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany
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Instituto Antofagasta, Universidad de Antofagasta, 1240000 Antofagasta, Chile
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Departamento Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, 4070386 Concepción, Chile
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Cells 2019, 8(11), 1333; https://doi.org/10.3390/cells8111333
Received: 26 August 2019 / Revised: 8 October 2019 / Accepted: 11 October 2019 / Published: 29 October 2019
Neurons release neurotransmitters at a specialized region of the presynaptic membrane, the active zone (AZ), where a complex meshwork of proteins organizes the release apparatus. The formation of this proteinaceous cytomatrix at the AZ (CAZ) depends on precise homo- and hetero-oligomerizations of distinct CAZ proteins. The CAZ protein CAST1/ERC2 contains four coiled-coil (CC) domains that interact with other CAZ proteins, but also promote self-assembly, which is an essential step for its integration during AZ formation. The self-assembly and synaptic recruitment of the Drosophila protein Bruchpilot (BRP), a partial homolog of CAST1/ERC2, is modulated by the serine-arginine protein kinase (SRPK79D). Here, we demonstrate that overexpression of the vertebrate SRPK2 regulates the self-assembly of CAST1/ERC2 in HEK293T, SH-SY5Y and HT-22 cells and the CC1 and CC4 domains are involved in this process. Moreover, the isoform SRPK2 forms a complex with CAST1/ERC2 when co-expressed in HEK293T and SH-SY5Y cells. More importantly, SRPK2 is present in brain synaptic fractions and synapses, suggesting that this protein kinase might control the level of self-aggregation of CAST1/ERC2 in synapses, and thereby modulate presynaptic assembly. View Full-Text
Keywords: active zone; CAST1/ERC2; coiled-coil; self-aggregation; SRPK; synapse active zone; CAST1/ERC2; coiled-coil; self-aggregation; SRPK; synapse
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Arancibia, D.; Lira, M.; Cruz, Y.; Barrera, D.P.; Montenegro-Venegas, C.; Godoy, J.A.; Garner, C.C.; Inestrosa, N.C.; Gundelfinger, E.D.; Zamorano, P.; Torres, V.I. Serine–Arginine Protein Kinase SRPK2 Modulates the Assembly of the Active Zone Scaffolding Protein CAST1/ERC2. Cells 2019, 8, 1333.

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